Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS), a genetic disorder that affects ~1 in 700 live births, is caused by trisomy of human chromosome 21 (Hsa21). Individuals with DS are affected by a wide spectrum of phenotypes which vary in severity and penetrance. However, cognitive and skeletal impairments can be commonly observed in all individuals with DS. To study these phenotypes, we utilized the Ts65Dn mouse model that carries three copies of approximately half the gene orthologs found on Hsa21 and exhibit similar phenotypes as observed in humans with DS. Individuals with DS and Ts65Dn mice have deficits in bone mineral density (BMD), bone architecture, bone strength, learning and memory. Over-expression of DYRK1A, a serine-threonine kinase encoded on Hsa21, has been linked to deficiencies in DS bone homeostasis and cognition. Epigallocatechin-3-gallate (EGCG), an aromatic polyphenol found in high concentrations in green tea, is a selective inhibitor of DYRK1A activity. Normalization of DYRK1A activity by EGCG therefore may have the potential to ameliorate skeletal and cognitive deficits. We hypothesized that supplements containing EGCG obtained from health food stores/ online vendors will not be as effective as EGCG from a chemical company in correcting bone deficits associated with DS. Our results suggest that EGCG improves the bone mineral density of trisomic femurs significantly better than the supplements while the EGCgNOW supplement from NOW FOODS improves trabecular and cortical bone structure. The results from HPLC analysis of supplements showed the presence of other catechins in EGCgNOW and degradation analysis revealed the rapid degradation of supplements. Therefore we hypothesize that the presence of EGCG degradation products and other green tea catechins in supplements may play a role in the differential skeletal effects we observed. We further hypothesized that a three week treatment of adolescent mice with EGCG will lead to an improvement in the learning and memory deficits that are observed in trisomic animals in comparison to control mice. However, our results indicate that three weeks of low-dose EGCG treatment during adolescence is insufficient to improve hippocampal dependent learning and memory deficits of Ts65Dn mice. The possibility remains that a higher dose of EGCG that begins at three weeks but lasts throughout the behavioral test period may result in improvement in learning and memory deficit of Ts65Dn mice.

Periodontal Ehlers-Danlos syndrome (pEDS) is a rare disorder caused by heterozygous mutations in complement 1 subunit genes C1R and C1S. To date, 148 cases have been described in the literature.We describe a case of a suspected de novo-mutation of pEDS with generalized Periapical cemental dysplasia (PCD) and cerebral leukoencephalopathy.

Objetivos: Avaliar a estatura final, mineralização e marcadores de mineralização óssea de adultos com síndrome nefrótica (SN) idiopática corticossensível na infância e adolescência e analisar a influência da doença, suas comorbidades e do alvo de estatura no crescimento e mineralização destes pacientes. Casuística: Avaliamos a estatura final de 60 pacientes (41 masculinos e 19 femininos) com idade mínima de dezenove anos ou desenvolvimento genital P4G4 nos masculinos e menarca nos femininos portadores de SN corticossensível na infância e adolescência. Realizamos a densitometria óssea (DMO=g/cm2) em 26 destes pacientes e em 35 controles, com análise concomitante dos níveis séricos de 25 OH vitamina D3 (25(OH)D), Paratormônio (PTH), telopéptido carboxiterminal do colágeno tipo 1( (CTx), Propeptídeo Aminoterminal do Colágeno Tipo I (P1NP) e Osteocalcina (OC) Resultados: A idade média inicial dos 60 pacientes foi de 5a3m e final de 20a5m, com acompanhamento médio de 15a2m. A dose média de prednisona utilizada foi de 1264 mg/kg. O Zscore médio da estatura inicial (-0,60; SD: 1,0) e final (0,64; SD: 0,92), não diferiu significativamente (Teste T: p=0,72) entre si. O Zscore estatura na idade adulta se correlacionou significativamente apenas com o Zscore estatura inicial e com o Zscore alvo de estatura. Seis pacientes atingiram Zscore estatura < -2 na idade adulta e este achado demonstrou forte correlação com o Zscore estatura inicial e com o Zscore alvo de estatura. A DMO e Zscore DMO de L1L4, Cabeça do fêmur e do Fêmur total dos pacientes e controles não diferiram significativamente. 6 pacientes e 2 controles apresentaram Zscore DMO < -2 (massa óssea reduzida) enquanto 2 pacientes e 1 controle demonstraram , Zscore DMO < -2,5 (osteoporose). Pacientes com massa óssea reduzida receberam 2189 mg/kg de prednisona durante 13 anos e aqueles com osteoporose, 2510 mg/kg durante 14 anos. Estes valores, comparados com aqueles de pacientes com massa óssea normal, mostraram significância estatística (p=0,01). Não houve correlação significativa entre as demais variáveis analisadas e a DMO. Os marcadores 25(OH)D, PTH, CTx, P1NP e OC dos pacientes e controles não diferiram significativamente. Quando analisados em relação à doença e suas comorbidades, DMO e estatura final não apresentaram significação estatística. Conclusões: 1. Os valores de Zscore estatura inicial e final se correlacionaram fortemente com o alvo de estatura. 2. Não houve associação entre as características clinicas da doença e a aquisição do alvo de estatura, neste grupo de pacientes. 3. A massa óssea e os marcadores de mineralização dos pacientes não diferiram quando comparados aos controles. 4. Os 6 pacientes com massa óssea reduzida (2 com osteoporose) utilizaram dose total e tempo de uso da prednisona significativamente maior que aqueles com massa óssea adequada 5. Não houve correlação entre os níveis séricos dos marcadores de mineralização óssea e a doença e suas comorbidades, a estatura final e a DMO dos pacientes adultos com SN na infância e adolescência / Objectives: The aim of the present study was to evaluate the final height, bone mineral density (BMD) and bone mineralization markers of adults with steroid responsive Idiopathic Nephrotic Syndrome (NS) in childhood and adolescence and to examine the influence of the disease, its co-morbidities and the patients\' target height in the final height and mineralization results. Patients and Methods: We have analyzed initial and final anthropometric data of 60 patients (41 male and 19 females) and / or their records, with a minimum age of nineteen years or fully developed pubertal status (P4G4 in males and menarche in females). BMD (g/cm2) was evaluated in 26 patients and in 35 controls, with a concomitant analysis, of serum levels of 25-OH Vitamin D (25(OH)D), Parathyroid Hormone (PTH); C-terminal telopeptide of type I collagen (CTx) and aminoterminal propeptide of type 1 procollagen (P1NP) and Osteocalcin (OC) Results: Mean age at first consultation was 5.3 years (SD: 2.4 yrs) and at last consultation was 20.4 yrs (SD: 3.0 yrs). The mean cumulative dose of prednisone was 1254 mg/kg (SD: 831.39 mg/kg). The mean initial height SDS was -0.60; (SD: 1.0) the final height SDS was -0.64; (SD: 0.92), (t-test: p=0.72). The final height SDS showed correlated significantly only with the initial height SDS and the target height SDS. Six patients achieved a final height SDS <-2 and this finding showed a strong correlation to the initial height SDS and to the target height SDS in the male patients. The patients\' and control subjects L1L4 head of the femur and the total femur BMD and BMD SDS did not differ significantly. 6 patients and 2 control subjects showed a BMD SDS <-2 (low bone mass) while 2 patients and 1 control subjects showed a BMD SDS <-2.5 (osteoporosis). Patients with BMD SDS <-2 received 2189 mg / kg of prednisone over 13 years while those with a BMD SDS <-2.5 received 2510 mg / kg prednisone for 14 years (p = 0.01 vs BMD SDS -2 ). No other studied variable correlated significantly with BMD. The studied bone biomarkers showed similar results in patients and control subjects without a significant correlation with disease activity, co-morbidities, and BMD or height parameters. Conclusion: 1. the initial and final height SDS were strongly correlated to the height target. 2. INS and its co-morbidities did not prevent the patients to reach their target height 3. The patients\' BMD and bone mineralization markers did not differ when compared to controls. 4. The 6 patients with low bone mass (2 with osteoporosis) used a total dose of prednisone for a longer period of time in relation to those with an adequate BMD 5. There was no correlation between bone mineralization markers, disease activity and its co-morbidities, final height and BMD of adult patients with INS in childhood and adolescence

Objetivos: Avaliar a estatura final, mineralização e marcadores de mineralização óssea de adultos com síndrome nefrótica (SN) idiopática corticossensível na infância e adolescência e analisar a influência da doença, suas comorbidades e do alvo de estatura no crescimento e mineralização destes pacientes. Casuística: Avaliamos a estatura final de 60 pacientes (41 masculinos e 19 femininos) com idade mínima de dezenove anos ou desenvolvimento genital P4G4 nos masculinos e menarca nos femininos portadores de SN corticossensível na infância e adolescência. Realizamos a densitometria óssea (DMO=g/cm2) em 26 destes pacientes e em 35 controles, com análise concomitante dos níveis séricos de 25 OH vitamina D3 (25(OH)D), Paratormônio (PTH), telopéptido carboxiterminal do colágeno tipo 1( (CTx), Propeptídeo Aminoterminal do Colágeno Tipo I (P1NP) e Osteocalcina (OC) Resultados: A idade média inicial dos 60 pacientes foi de 5a3m e final de 20a5m, com acompanhamento médio de 15a2m. A dose média de prednisona utilizada foi de 1264 mg/kg. O Zscore médio da estatura inicial (-0,60; SD: 1,0) e final (0,64; SD: 0,92), não diferiu significativamente (Teste T: p=0,72) entre si. O Zscore estatura na idade adulta se correlacionou significativamente apenas com o Zscore estatura inicial e com o Zscore alvo de estatura. Seis pacientes atingiram Zscore estatura < -2 na idade adulta e este achado demonstrou forte correlação com o Zscore estatura inicial e com o Zscore alvo de estatura. A DMO e Zscore DMO de L1L4, Cabeça do fêmur e do Fêmur total dos pacientes e controles não diferiram significativamente. 6 pacientes e 2 controles apresentaram Zscore DMO < -2 (massa óssea reduzida) enquanto 2 pacientes e 1 controle demonstraram , Zscore DMO < -2,5 (osteoporose). Pacientes com massa óssea reduzida receberam 2189 mg/kg de prednisona durante 13 anos e aqueles com osteoporose, 2510 mg/kg durante 14 anos. Estes valores, comparados com aqueles de pacientes com massa óssea normal, mostraram significância estatística (p=0,01). Não houve correlação significativa entre as demais variáveis analisadas e a DMO. Os marcadores 25(OH)D, PTH, CTx, P1NP e OC dos pacientes e controles não diferiram significativamente. Quando analisados em relação à doença e suas comorbidades, DMO e estatura final não apresentaram significação estatística. Conclusões: 1. Os valores de Zscore estatura inicial e final se correlacionaram fortemente com o alvo de estatura. 2. Não houve associação entre as características clinicas da doença e a aquisição do alvo de estatura, neste grupo de pacientes. 3. A massa óssea e os marcadores de mineralização dos pacientes não diferiram quando comparados aos controles. 4. Os 6 pacientes com massa óssea reduzida (2 com osteoporose) utilizaram dose total e tempo de uso da prednisona significativamente maior que aqueles com massa óssea adequada 5. Não houve correlação entre os níveis séricos dos marcadores de mineralização óssea e a doença e suas comorbidades, a estatura final e a DMO dos pacientes adultos com SN na infância e adolescência / Objectives: The aim of the present study was to evaluate the final height, bone mineral density (BMD) and bone mineralization markers of adults with steroid responsive Idiopathic Nephrotic Syndrome (NS) in childhood and adolescence and to examine the influence of the disease, its co-morbidities and the patients\' target height in the final height and mineralization results. Patients and Methods: We have analyzed initial and final anthropometric data of 60 patients (41 male and 19 females) and / or their records, with a minimum age of nineteen years or fully developed pubertal status (P4G4 in males and menarche in females). BMD (g/cm2) was evaluated in 26 patients and in 35 controls, with a concomitant analysis, of serum levels of 25-OH Vitamin D (25(OH)D), Parathyroid Hormone (PTH); C-terminal telopeptide of type I collagen (CTx) and aminoterminal propeptide of type 1 procollagen (P1NP) and Osteocalcin (OC) Results: Mean age at first consultation was 5.3 years (SD: 2.4 yrs) and at last consultation was 20.4 yrs (SD: 3.0 yrs). The mean cumulative dose of prednisone was 1254 mg/kg (SD: 831.39 mg/kg). The mean initial height SDS was -0.60; (SD: 1.0) the final height SDS was -0.64; (SD: 0.92), (t-test: p=0.72). The final height SDS showed correlated significantly only with the initial height SDS and the target height SDS. Six patients achieved a final height SDS <-2 and this finding showed a strong correlation to the initial height SDS and to the target height SDS in the male patients. The patients\' and control subjects L1L4 head of the femur and the total femur BMD and BMD SDS did not differ significantly. 6 patients and 2 control subjects showed a BMD SDS <-2 (low bone mass) while 2 patients and 1 control subjects showed a BMD SDS <-2.5 (osteoporosis). Patients with BMD SDS <-2 received 2189 mg / kg of prednisone over 13 years while those with a BMD SDS <-2.5 received 2510 mg / kg prednisone for 14 years (p = 0.01 vs BMD SDS -2 ). No other studied variable correlated significantly with BMD. The studied bone biomarkers showed similar results in patients and control subjects without a significant correlation with disease activity, co-morbidities, and BMD or height parameters. Conclusion: 1. the initial and final height SDS were strongly correlated to the height target. 2. INS and its co-morbidities did not prevent the patients to reach their target height 3. The patients\' BMD and bone mineralization markers did not differ when compared to controls. 4. The 6 patients with low bone mass (2 with osteoporosis) used a total dose of prednisone for a longer period of time in relation to those with an adequate BMD 5. There was no correlation between bone mineralization markers, disease activity and its co-morbidities, final height and BMD of adult patients with INS in childhood and adolescence

Introdução: raquitismo e osteomalácia hipofosfatêmicos de origem genética mediados por FGF23 (RQ/OM-FGF23) são caracterizados pelo aumento patológico dos níveis séricos de FGF23 com consequentes hiperfosfatúria e hipofosfatemia. A forma hereditária mais comum é a ligada ao X dominante (XLHR) ocasionada por mutações inativadoras no gene PHEX. Objetivos: identificar a etiologia molecular; avaliar a densidade mineral óssea (DMO) e a microarquitetura óssea e, determinar a prevalência de nefrocalcinose (NC), nefrolitíase (NL) e de alterações metabólicas urinárias em 47 pacientes com RQ/OM-FGF23 (16 crianças e 31 adultos). Métodos: as análises dos genes PHEX e FGF23 foram realizadas pelos métodos de Sanger e MLPA. A DMO areal (DMOa) foi avaliada por densitometria óssea (DXA), enquanto a DMO volumétrica (DMOv) e os parâmetros de microarquitetura óssea foram analisados por HR-pQCT. A NC foi classificada segundo uma escala de 0-3 (0 = ausência de NC; 3 = NC grave) pelas ultrassonografia (US) e tomografia computadorizada (TC) renais. A presença de NL foi analisada pela TC renal. Fatores de risco para NC e NL foram avaliados pela urina de 24 horas. Resultados: foram identificadas mutações no PHEX em 41 pacientes (87,2%). A avaliação óssea foi realizada em 38 pacientes com XLHR que foram comparados a controles saudáveis. Os pacientes tiveram maior DMOa em L1-L4 (p=0,03) e menor DMOa em 1/3 distal do rádio (p < 0,01). Em rádio distal, a DMOv total (Total.vBMD) e os componentes trabecular (Tb.vBMD) e cortical (Ct.vBMD) foram semelhantes entre os grupos. Na tíbia distal, os pacientes apresentaram menor Total.vBMD em relação aos controles devido ao déficit no Tb.vBMD (p < 0,01). Além do mais, ao separarmos por status metabólico, os pacientes descompensados tiveram menor Ct.vBMD em tíbia distal comparados aos controles (p=0,02). Quanto aos parâmetros estruturais, em rádio distal, os pacientes apresentaram menor número de trabéculas (Tb.N; p=0,01), maior espessura trabecular (Tb.Th; p < 0,01) e maior falta da homogeneidade trabecular (SD.1/Tb.N; p=0,02). Na tíbia distal, eles tiveram menor Tb.N (p < 0,01), maior separação trabecular (Tb.Sp; p < 0,01) e maior SD.1/Tb.N (p < 0,01). A avaliação renal foi feita em 39 pacientes com XLHR. A NC foi diagnosticada em 15 (38,5%) pacientes pelas US e TC, principalmente no grupo pediátrico em uso intensivo de fosfato. A US detectou NC em 37 (94,8%), majoritariamente como grau 1 (97%), enquanto a TC identificou NC medular em 15 (38,5%): 10 (66,7%) como grau 1 e cinco (33,3%) como grau 2. Quatro (10,2%) pacientes adultos tinham NL determinada pela CT. Além da hiperfosfatúria presente em todos os pacientes, a hipocitratúria foi a alteração metabólica mais comum (30,7%); somente dois pacientes apresentaram hipercalciúria (5,1%) e nenhum apresentou hiperoxalúria. Conclusões: nesta casuística, a XLHR foi a principal forma hereditária de RQ/OM-FGF23. A HR-pQCT foi mais informativa do que a DXA e o compartimento ósseo trabecular foi mais afetado pela doença, particularmente na tíbia distal. Finalmente, a NC foi mais prevalente que a NL; o principal fator de risco metabólico foi a hiperfosfatúria e o tratamento intensivo com fosfato parece ser um agravante na formação da NC / Background: FGF23-mediated hypophosphatemic rickets is a group of diseases characterized by a pathological increase of FGF23 serum levels, resulting in hyperphosphaturia and hypophosphatemia. In this group, the most common form of inheritance is the X-linked dominant (XLHR) caused by inactivating mutations in the PHEX gene. Aims: to identify the molecular basis; to evaluate the bone mineral density and bone microarchitecture; to determinate the prevalence of nephrocalcinosis (NC), nephrolithiasis (NL) and their related metabolic factors in 47 patients with FGF23-mediated hypophosphatemic rickets (16 children and 31 adults). Methods: PHEX and FGF23 were analyzed by conventional Sanger sequencing and MLPA. The areal BMD (aBMD) was evaluated by dual-energy x-ray absorptiometry (DXA), while the volumetric BMD (vBMD) and the bone microarchitecture were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). NC was investigated by renal ultrasonography (US) and computed tomography (CT) and classified using a 0-3 scale (0= no NC and 3= severe NC). The presence of NL was determined by renal CT. Risk factors for NC and NL were evaluated by 24-hour urinary samples. Results: 41 patients (87.2%) presented mutations in PHEX. The bone analysis was made in 38 XLHR patients compared to healthy controls. XLHR patients presented higher aBMD at L1-L4 (p=0.03) and lower aBMD at the distal third of the radius (p < 0.01). At the distal radius, HR-pQCT showed no differences in the vBMD neither in its trabecular (Tb.vBMD) and cortical (Ct.vBMD) components. At the distal tibia, the XLHR patients showed lower Total.vBMD (p < 0.01) compared to controls due to decreased Tb.vBMD (p < 0.01). Moreover, after XLHR patients were sorted by metabolic status, the noncompensated ones revealed lower Ct.vBMD at the distal tibia compared to their respective controls (p=0.02). Regarding to the microarchitectural parameters, at the distal radius, XLHR patients showed lower trabecular number (Tb.N; p=0.01), greater trabecular thickness (Tb.Th; p < 0.01) and more inhomogeneous trabecular network (SD.1/Tb.N; p=0.02). At the distal tibia, they had lower Tb.N (p < 0.01), larger trabecular separation (Tb.Sp; p < 0.01) and greater SD.1/Tb.N (p < 0.01). The renal assessment was done in 39 XLHR patients. NC was diagnosed in 15 (38.5%) patients by US and CT, mainly in the pediatric group that was in phosphate treatment. US identified NC in 37 (94.8%), mostly as grade 1 (97%), meanwhile CT determined medullary NC in 15 (38.5%) patients: 10 (66.7%) as grade 1 and five (33.3%) as grade 2. Four (10.2%) adults patients had NL determined by CT. Besides hyperphosphaturia present in all XLHR patients, hypocitraturia was the most common metabolic factor (30.7%); hypercalciuria occurred in only two patients (5.1%) and none had hyperoxaluria. Conclusions: in our cohort, XLHR was the most prevalent form of FGF23-mediated inherited hypophosphatemic rickets. HR-pQCT was more informative than DXA and the cancellous bone compartment was the most affected by the disease particularly at the distal tibia. Finally, NC was more prevalent than NL; the main metabolic risk factor was hyperphosphaturia and the intensive treatment with phosphate seems to be an aggravating factor in the formation of NC

Introdução: raquitismo e osteomalácia hipofosfatêmicos de origem genética mediados por FGF23 (RQ/OM-FGF23) são caracterizados pelo aumento patológico dos níveis séricos de FGF23 com consequentes hiperfosfatúria e hipofosfatemia. A forma hereditária mais comum é a ligada ao X dominante (XLHR) ocasionada por mutações inativadoras no gene PHEX. Objetivos: identificar a etiologia molecular; avaliar a densidade mineral óssea (DMO) e a microarquitetura óssea e, determinar a prevalência de nefrocalcinose (NC), nefrolitíase (NL) e de alterações metabólicas urinárias em 47 pacientes com RQ/OM-FGF23 (16 crianças e 31 adultos). Métodos: as análises dos genes PHEX e FGF23 foram realizadas pelos métodos de Sanger e MLPA. A DMO areal (DMOa) foi avaliada por densitometria óssea (DXA), enquanto a DMO volumétrica (DMOv) e os parâmetros de microarquitetura óssea foram analisados por HR-pQCT. A NC foi classificada segundo uma escala de 0-3 (0 = ausência de NC; 3 = NC grave) pelas ultrassonografia (US) e tomografia computadorizada (TC) renais. A presença de NL foi analisada pela TC renal. Fatores de risco para NC e NL foram avaliados pela urina de 24 horas. Resultados: foram identificadas mutações no PHEX em 41 pacientes (87,2%). A avaliação óssea foi realizada em 38 pacientes com XLHR que foram comparados a controles saudáveis. Os pacientes tiveram maior DMOa em L1-L4 (p=0,03) e menor DMOa em 1/3 distal do rádio (p < 0,01). Em rádio distal, a DMOv total (Total.vBMD) e os componentes trabecular (Tb.vBMD) e cortical (Ct.vBMD) foram semelhantes entre os grupos. Na tíbia distal, os pacientes apresentaram menor Total.vBMD em relação aos controles devido ao déficit no Tb.vBMD (p < 0,01). Além do mais, ao separarmos por status metabólico, os pacientes descompensados tiveram menor Ct.vBMD em tíbia distal comparados aos controles (p=0,02). Quanto aos parâmetros estruturais, em rádio distal, os pacientes apresentaram menor número de trabéculas (Tb.N; p=0,01), maior espessura trabecular (Tb.Th; p < 0,01) e maior falta da homogeneidade trabecular (SD.1/Tb.N; p=0,02). Na tíbia distal, eles tiveram menor Tb.N (p < 0,01), maior separação trabecular (Tb.Sp; p < 0,01) e maior SD.1/Tb.N (p < 0,01). A avaliação renal foi feita em 39 pacientes com XLHR. A NC foi diagnosticada em 15 (38,5%) pacientes pelas US e TC, principalmente no grupo pediátrico em uso intensivo de fosfato. A US detectou NC em 37 (94,8%), majoritariamente como grau 1 (97%), enquanto a TC identificou NC medular em 15 (38,5%): 10 (66,7%) como grau 1 e cinco (33,3%) como grau 2. Quatro (10,2%) pacientes adultos tinham NL determinada pela CT. Além da hiperfosfatúria presente em todos os pacientes, a hipocitratúria foi a alteração metabólica mais comum (30,7%); somente dois pacientes apresentaram hipercalciúria (5,1%) e nenhum apresentou hiperoxalúria. Conclusões: nesta casuística, a XLHR foi a principal forma hereditária de RQ/OM-FGF23. A HR-pQCT foi mais informativa do que a DXA e o compartimento ósseo trabecular foi mais afetado pela doença, particularmente na tíbia distal. Finalmente, a NC foi mais prevalente que a NL; o principal fator de risco metabólico foi a hiperfosfatúria e o tratamento intensivo com fosfato parece ser um agravante na formação da NC / Background: FGF23-mediated hypophosphatemic rickets is a group of diseases characterized by a pathological increase of FGF23 serum levels, resulting in hyperphosphaturia and hypophosphatemia. In this group, the most common form of inheritance is the X-linked dominant (XLHR) caused by inactivating mutations in the PHEX gene. Aims: to identify the molecular basis; to evaluate the bone mineral density and bone microarchitecture; to determinate the prevalence of nephrocalcinosis (NC), nephrolithiasis (NL) and their related metabolic factors in 47 patients with FGF23-mediated hypophosphatemic rickets (16 children and 31 adults). Methods: PHEX and FGF23 were analyzed by conventional Sanger sequencing and MLPA. The areal BMD (aBMD) was evaluated by dual-energy x-ray absorptiometry (DXA), while the volumetric BMD (vBMD) and the bone microarchitecture were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). NC was investigated by renal ultrasonography (US) and computed tomography (CT) and classified using a 0-3 scale (0= no NC and 3= severe NC). The presence of NL was determined by renal CT. Risk factors for NC and NL were evaluated by 24-hour urinary samples. Results: 41 patients (87.2%) presented mutations in PHEX. The bone analysis was made in 38 XLHR patients compared to healthy controls. XLHR patients presented higher aBMD at L1-L4 (p=0.03) and lower aBMD at the distal third of the radius (p < 0.01). At the distal radius, HR-pQCT showed no differences in the vBMD neither in its trabecular (Tb.vBMD) and cortical (Ct.vBMD) components. At the distal tibia, the XLHR patients showed lower Total.vBMD (p < 0.01) compared to controls due to decreased Tb.vBMD (p < 0.01). Moreover, after XLHR patients were sorted by metabolic status, the noncompensated ones revealed lower Ct.vBMD at the distal tibia compared to their respective controls (p=0.02). Regarding to the microarchitectural parameters, at the distal radius, XLHR patients showed lower trabecular number (Tb.N; p=0.01), greater trabecular thickness (Tb.Th; p < 0.01) and more inhomogeneous trabecular network (SD.1/Tb.N; p=0.02). At the distal tibia, they had lower Tb.N (p < 0.01), larger trabecular separation (Tb.Sp; p < 0.01) and greater SD.1/Tb.N (p < 0.01). The renal assessment was done in 39 XLHR patients. NC was diagnosed in 15 (38.5%) patients by US and CT, mainly in the pediatric group that was in phosphate treatment. US identified NC in 37 (94.8%), mostly as grade 1 (97%), meanwhile CT determined medullary NC in 15 (38.5%) patients: 10 (66.7%) as grade 1 and five (33.3%) as grade 2. Four (10.2%) adults patients had NL determined by CT. Besides hyperphosphaturia present in all XLHR patients, hypocitraturia was the most common metabolic factor (30.7%); hypercalciuria occurred in only two patients (5.1%) and none had hyperoxaluria. Conclusions: in our cohort, XLHR was the most prevalent form of FGF23-mediated inherited hypophosphatemic rickets. HR-pQCT was more informative than DXA and the cancellous bone compartment was the most affected by the disease particularly at the distal tibia. Finally, NC was more prevalent than NL; the main metabolic risk factor was hyperphosphaturia and the intensive treatment with phosphate seems to be an aggravating factor in the formation of NC

Indiana University-Purdue University Indianapolis (IUPUI) / Signal Transducer and Activator of Transcription 3 (STAT3) is known to be related to bone metabolism. Mutation of STAT3 causes a rare disorder in which serum levels of IgE are elevated. This causes various skeletal problems similar to osteoporosis. To examine the effect of STAT3 in the osteoclast, we obtained two osteoclast specific STAT3 knockout mouse models: one using the CTSK promoter to drive Cre recombinase and another using a TRAP promoter. Examination of these mice at 8 weeks of age revealed a decreased trabecular bone volume in CTSK specific STAT3 knockout mice along with a slight decrease in osteoclast number in both CTSK and TRAP specific STAT3 knockout females. We also noticed changes in bone mineral density and bone mechanical strength in females. These data suggest that STAT3 plays a part in the function of the osteoclast.

Holz aus Kurzumtriebsplantagen (KUP) mit Pappeln (Populus spp.) kann eine bedeutende Rolle im Mix der Bioenergieressourcen in Deutschland spielen. Trotz eines günstigen Energieinput-Energieoutput-Verhältnisses ist das Erreichen wirtschaftlich zufriedenstellender Ergebnisse mit KUP jedoch auf den meisten potenziellen Anbauflächen durch hohe Ansprüche der Pappeln an die Wasserversorgung erschwert. Hohe Produktivitätsraten der Pappeln sind an einen hohen Wasserverbrauch gebunden und viele Trockenheitsanpassungen führen zu deutlichen Ertragsrückgängen. In der vorgestellten Arbeit wurde eine sechsjährige Vollgeschwister-F1-Kartierungspopulation der Europäischen Zitter Pappel (Aspe, Populus tremula L., Wuchsperiode 1998-2003) physiologisch und genetisch untersucht, um mögliche Wege zu einer züchterischen Verbesserung der Trockenheitstoleranz von Pappeln diskutieren zu können. Dabei wurde das Zuchtziel der Trockenheitstoleranz als Minimierung der Ertragsrückgänge unter trockenen Bedingungen definiert. Neben wuchsleistungsbezogenen Größen (Biomassegesamtleistung (BM, oberirdische Dendromasse), Biomassezuwachs (iBM), Radialzuwachs (ir), Baumhöhe (h)) wurden physiologisch holzanatomische Eigenschaften untersucht, die retrospektiv anhand der Jahrringe messbar sind und zur nicht direkt messbaren Eigenschaft der Trockenheitstoleranz in einer Beziehung stehen. Diese waren die Kohlenstoff- und Sauerstoffisotopsignatur (δ13C, δ18O), die Faser- und Gefäßgliedlänge (FL, GL), die Gefäßlumenquerschnittsfläche (AG), die Gefäßdichte (GD), der potenziell Saftstrom leitende Querschnittsflächenanteil (LQ), der hydraulisch gewichtete Gefäßlumendurchmesser (Dh) und die röntgendensitometrische Holzdichte (RD). Um trockenheitsbedingte physiologische Reaktionen vom Einfluss der Juvenilität der Kartierungspopulation unterscheiden zu können, wurden regionaltypische Juvenilitätstrends der RD, FL, GL, und des ir anhand eines zweiten, für das östliche Deutschland repräsentativen Aspen-Kollektivs aus natürlicher Sukzession ermittelt. Bedingt durch Trockenheitsanpassungen bzw. eine bevorzugte Wurzelentwicklung nach dem Verpflanzen zeigte die Kartierungspopulation in den ersten drei Jahrringen Abweichungen von den regionaltypischen Juvenilitätstrends. In den Trendverläufen der Kartierungspopulation heben sich die beiden Trockenvegetationsperioden 2000 und 2003 ab, wobei bis zum Sommer 2003 infolge des Starkniederschlages 2002 (Flut) ein außergewöhnlich gutes Grundwasserangebot herrschte. Alle untersuchten phänotypischen Eigenschaften zeigten 2000 starke trockenheitsbedingte Abweichungen. Im Jahrring 2003 wichen nur die GL und die RD von ihren Juvenilitätstrends ab. Außerdem konnte anhand der δ13C und δ18O Werte eine signifikante Abnahme der Wassernutzungseffizienz bzw. eine Zunahme der Transpiration im Jahr 2003 gezeigt werden. Die übrigen Größen folgten ihren Juvenilitätstrends und stiegen an. Die Jahrringdatensätze 2000 und 2003 der RD waren nicht signifikant mit der BM korreliert, dagegen zeigten die δ13C Datensätze 2002 und 2003 schwach positive Korrelationen mit der BM. Der trockenheitstoleranteste Genotyp verband seine überdurchschnittliche BM mit einer hohen Wassernutzungseffizienz (angezeigt durch überdurchschnittliche δ13C Werte), mit einer überdurchschnittlichen AG und mit einer nicht unterdurchschnittlichen RD in Höhe des Populationsmittels. Aufgrund des Fehlens negativer Korrelationen zwischen BM und δ13C bzw. BM und RD in der vorliegenden Arbeit können δ13C und RD als nützliche Weiser für die Unterscheidung der Trockenheitstoleranz verschiedener Aspen zu züchterischen Zwecken vorgeschlagen werden. Außer der BM unter trockenen Bedingungen kann keine der untersuchten Eigenschaften als alleiniger Trockenheitstoleranzweiser empfohlen werden. Zu einer Trockenheitstoleranzbewertung sollten Merkmalspaare verwendet werden, von denen ein Merkmal positiv mit dem Ertrag korreliert ist und das andere eine Trockenheitsanpassung verkörpert. Dadurch werden sowohl das primäre Zuchtziel eines höchstmöglichen Ertrages als auch eine bessere Trockenheitsangepasstheit berücksichtigt. Zwei verschiedene Trockenheitstoleranzindizierungen wurden angewendet, um die Kartierungsnachkommen entsprechend ihrer Trockenheitstoleranz einem Ranking zu unterziehen. Dabei wurden in beiden Fällen Bäume mit einem höheren Ertrag besser platziert. Der zweite Schwerpunkt der Arbeit lag auf der genetischen Kartierung von Quantitative Trait Loci (QTL) für die untersuchten phänotypischen Jahrringeigenschaften mit Bezug zur Trockenheitstoleranz. Als Basis für das QTL Mapping wurden, der Pseudo-Testcross-Mapping-Strategie folgend, genetische Kopplungskarten für die Elternbäume der Kartierungspopulation konstruiert. Die maternale Karte (P. tremula, „Schandau 4“) deckte mit 157 Markern (144 AFLP, 13 SSR) in 30 Kopplungsgruppen 1.369 cM ab, die 21 paternalen Kopplungsgruppen mit 148 Markern (132 AFLP, 16 SSR) überspannten 1.079 cM des Genoms (P. tremula, „Lichtenhain 1“). Die im Vergleich zur haploiden Chromosomenzahl der Pappeln (19) hohen Zahlen an Kopplungsgruppen sowie die hohen Zahlen an Doublets und unkartierten Markern zeigten eine geringe Genomabdeckung an. So konnte nur eine begrenzte Zahl, höchstens zwei QTL für die untersuchten phänotypischen Jahrringeigenschaften mit Bezug zur Trockenheitstoleranz, kartiert werden. Ein QTL Bereich mit pleiotropem Effekt auf mehrere wachstumsbezogene Größen wurde auf der maternalen Kopplungsgruppe 1 (dem Populus Chromosom I zuzuordnen) detektiert. Die Signifikanz der Effekte dieses QTL auf den Radialzuwachs entwickelte sich steigend mit zunehmendem Baumalter. / Wood production in short rotation coppices (SRC) with poplar (Populus spp.) can contribute significantly to the future bio energy supply mix in Germany. Although the energy-input to energy-output ratio is rather good, SRC often do not meet cost effectiveness due to high water demand of poplar species. High biomass productivity depends on optimal water supply. Also, numerous adaptations to water deficits result in an undesirable decrease of yield. Combined physiological and genetic investigations were conducted within a six-year old F1-full-sib crossbred population of European aspen (Populus tremula L., growing period 1998-2003). Possible implications on selection, breeding or improvement of poplar cultivars showing a high tolerance to water deficits are discussed. For the work presented here, the breeding goal of higher water deficit tolerance was defined as the minimisation of yield losses under dry conditions. Beyond growth related traits (aggregate yield (BM), aboveground woody biomass), biomass increment (iBM) and radial increment (ir), physiological and wood anatomical traits were included; these are related to reactions to water deficit and are measurable on tree rings retrospectively. These traits were the Carbon- and Oxygen isotope ratios (δ13C, δ18O), the fibre length and vessel element length (FL, GL), the vessel lumen cross sectional area (AG), the vessel density (GD), the cumulative vessel lumen area to cross sectional area ratio (LQ), the hydraulically weighted mean vessel lumen diameter (Dh) and wood density assessed by X-ray densitometry (RD). To distinguish the drought induced physiologic reactions from juvenile developmental patterns of the mapping population, juvenile trends of RD, FL, GL, and ir, which are representative of habitats in south-eastern Germany, were investigated in a second aspen collective that was selected from natural succession. During the first three years, the mapping population showed deviations from the juvenile trends due to water deficit adaptations or preferential root development, respectively. Due to drought in the growing seasons of 2000 and 2003, the juvenile trends show outstanding values for both years, although ground water supply in 2003 was exceptionally good following the intense rain event of 2002 (Elbe flood 2002). The tree ring traits of both years stand out from the juvenile trends due to drought adaptations. In 2000, all phenotypic traits showed a significant deviation from their respective trends. In 2003, only GL and RD showed an adaptation to drought as observable by a deviation from their juvenile trends. A significant decrease in water use efficiency (WUE) and an increase in net transpiration, respectively, were shown for 2003 by means of δ13C or δ18O values. All other traits showed an increase following their juvenile trends. RD data for 2000 and 2003 were not significantly correlated with BM, but δ13C data (and therefore WUE) for 2002 and 2003 revealed a weakly positive correlation with BM. The genotype that was most tolerant to water deficits showed a combination of a superior growth with a superior WUE (by means of δ13C), a superior AG, and an RD close to but not less than the population average. Due to the lack of negative correlation between BM and δ13C or BM and RD in the present work, δ13C and RD can be valuable proxies for the determination of drought tolerance of aspen trees for tree improvement purposes. Aside from BM under dry conditions, no other traits that were investigated can be recommended as a stand-alone proxy for water deficit tolerance. For a water deficit tolerance evaluation, pairs of traits should be used, of which one trait is positively correlated with yield and the other represents a water deficit adaptation. Both the primary breeding goal of the highest possible yield as well as a better water deficit tolerance should always be considered in this context. Two different drought tolerance indices were used to rank the individuals of the mapping population according to their water deficit tolerance. In both cases, trees with higher BM were ranked better. The second focus of the present work is on genetic mapping of Quantitative Trait Loci (QTL) for the investigated tree-ring traits that refer to water deficit reaction. As a basis for the QTL-mapping approach, genetic linkage maps were constructed for each parental tree of the F1-full-sib crossbred mapping-population following the two-way pseudo-testcross mapping strategy. The maternal map (P. tremula, “Schandau 4”) consisted of 157 markers (144 AFLP, 13 SSR) in 30 linkage groups and covered 1,369 cM. The 21 linkage groups of the paternal map (P. tremula, “Lichtenhain 1”) covered 1,079 cM of the genome (144 AFLP, 13 SSR). Compared with the haploid chromosome number (19) of the Populus genome, the high number of linkage groups, doublets and unlinked markers indicated low genome coverage. Only a low number of QTL was detected, maximal two per in¬vesti¬gated phenotypic trait with a relation to water deficit tolerance. One QTL having a pleiotropic effect on several growth related traits was detected on the maternal linkage group 1 (corresponding to the Populus Chromosome I). The significance of the QTL effects seemed to increase with tree age.

Holz aus Kurzumtriebsplantagen (KUP) mit Pappeln (Populus spp.) kann eine bedeutende Rolle im Mix der Bioenergieressourcen in Deutschland spielen. Trotz eines günstigen Energieinput-Energieoutput-Verhältnisses ist das Erreichen wirtschaftlich zufriedenstellender Ergebnisse mit KUP jedoch auf den meisten potenziellen Anbauflächen durch hohe Ansprüche der Pappeln an die Wasserversorgung erschwert. Hohe Produktivitätsraten der Pappeln sind an einen hohen Wasserverbrauch gebunden und viele Trockenheitsanpassungen führen zu deutlichen Ertragsrückgängen. In der vorgestellten Arbeit wurde eine sechsjährige Vollgeschwister-F1-Kartierungspopulation der Europäischen Zitter Pappel (Aspe, Populus tremula L., Wuchsperiode 1998-2003) physiologisch und genetisch untersucht, um mögliche Wege zu einer züchterischen Verbesserung der Trockenheitstoleranz von Pappeln diskutieren zu können. Dabei wurde das Zuchtziel der Trockenheitstoleranz als Minimierung der Ertragsrückgänge unter trockenen Bedingungen definiert. Neben wuchsleistungsbezogenen Größen (Biomassegesamtleistung (BM, oberirdische Dendromasse), Biomassezuwachs (iBM), Radialzuwachs (ir), Baumhöhe (h)) wurden physiologisch holzanatomische Eigenschaften untersucht, die retrospektiv anhand der Jahrringe messbar sind und zur nicht direkt messbaren Eigenschaft der Trockenheitstoleranz in einer Beziehung stehen. Diese waren die Kohlenstoff- und Sauerstoffisotopsignatur (δ13C, δ18O), die Faser- und Gefäßgliedlänge (FL, GL), die Gefäßlumenquerschnittsfläche (AG), die Gefäßdichte (GD), der potenziell Saftstrom leitende Querschnittsflächenanteil (LQ), der hydraulisch gewichtete Gefäßlumendurchmesser (Dh) und die röntgendensitometrische Holzdichte (RD). Um trockenheitsbedingte physiologische Reaktionen vom Einfluss der Juvenilität der Kartierungspopulation unterscheiden zu können, wurden regionaltypische Juvenilitätstrends der RD, FL, GL, und des ir anhand eines zweiten, für das östliche Deutschland repräsentativen Aspen-Kollektivs aus natürlicher Sukzession ermittelt. Bedingt durch Trockenheitsanpassungen bzw. eine bevorzugte Wurzelentwicklung nach dem Verpflanzen zeigte die Kartierungspopulation in den ersten drei Jahrringen Abweichungen von den regionaltypischen Juvenilitätstrends. In den Trendverläufen der Kartierungspopulation heben sich die beiden Trockenvegetationsperioden 2000 und 2003 ab, wobei bis zum Sommer 2003 infolge des Starkniederschlages 2002 (Flut) ein außergewöhnlich gutes Grundwasserangebot herrschte. Alle untersuchten phänotypischen Eigenschaften zeigten 2000 starke trockenheitsbedingte Abweichungen. Im Jahrring 2003 wichen nur die GL und die RD von ihren Juvenilitätstrends ab. Außerdem konnte anhand der δ13C und δ18O Werte eine signifikante Abnahme der Wassernutzungseffizienz bzw. eine Zunahme der Transpiration im Jahr 2003 gezeigt werden. Die übrigen Größen folgten ihren Juvenilitätstrends und stiegen an. Die Jahrringdatensätze 2000 und 2003 der RD waren nicht signifikant mit der BM korreliert, dagegen zeigten die δ13C Datensätze 2002 und 2003 schwach positive Korrelationen mit der BM. Der trockenheitstoleranteste Genotyp verband seine überdurchschnittliche BM mit einer hohen Wassernutzungseffizienz (angezeigt durch überdurchschnittliche δ13C Werte), mit einer überdurchschnittlichen AG und mit einer nicht unterdurchschnittlichen RD in Höhe des Populationsmittels. Aufgrund des Fehlens negativer Korrelationen zwischen BM und δ13C bzw. BM und RD in der vorliegenden Arbeit können δ13C und RD als nützliche Weiser für die Unterscheidung der Trockenheitstoleranz verschiedener Aspen zu züchterischen Zwecken vorgeschlagen werden. Außer der BM unter trockenen Bedingungen kann keine der untersuchten Eigenschaften als alleiniger Trockenheitstoleranzweiser empfohlen werden. Zu einer Trockenheitstoleranzbewertung sollten Merkmalspaare verwendet werden, von denen ein Merkmal positiv mit dem Ertrag korreliert ist und das andere eine Trockenheitsanpassung verkörpert. Dadurch werden sowohl das primäre Zuchtziel eines höchstmöglichen Ertrages als auch eine bessere Trockenheitsangepasstheit berücksichtigt. Zwei verschiedene Trockenheitstoleranzindizierungen wurden angewendet, um die Kartierungsnachkommen entsprechend ihrer Trockenheitstoleranz einem Ranking zu unterziehen. Dabei wurden in beiden Fällen Bäume mit einem höheren Ertrag besser platziert. Der zweite Schwerpunkt der Arbeit lag auf der genetischen Kartierung von Quantitative Trait Loci (QTL) für die untersuchten phänotypischen Jahrringeigenschaften mit Bezug zur Trockenheitstoleranz. Als Basis für das QTL Mapping wurden, der Pseudo-Testcross-Mapping-Strategie folgend, genetische Kopplungskarten für die Elternbäume der Kartierungspopulation konstruiert. Die maternale Karte (P. tremula, „Schandau 4“) deckte mit 157 Markern (144 AFLP, 13 SSR) in 30 Kopplungsgruppen 1.369 cM ab, die 21 paternalen Kopplungsgruppen mit 148 Markern (132 AFLP, 16 SSR) überspannten 1.079 cM des Genoms (P. tremula, „Lichtenhain 1“). Die im Vergleich zur haploiden Chromosomenzahl der Pappeln (19) hohen Zahlen an Kopplungsgruppen sowie die hohen Zahlen an Doublets und unkartierten Markern zeigten eine geringe Genomabdeckung an. So konnte nur eine begrenzte Zahl, höchstens zwei QTL für die untersuchten phänotypischen Jahrringeigenschaften mit Bezug zur Trockenheitstoleranz, kartiert werden. Ein QTL Bereich mit pleiotropem Effekt auf mehrere wachstumsbezogene Größen wurde auf der maternalen Kopplungsgruppe 1 (dem Populus Chromosom I zuzuordnen) detektiert. Die Signifikanz der Effekte dieses QTL auf den Radialzuwachs entwickelte sich steigend mit zunehmendem Baumalter. / Wood production in short rotation coppices (SRC) with poplar (Populus spp.) can contribute significantly to the future bio energy supply mix in Germany. Although the energy-input to energy-output ratio is rather good, SRC often do not meet cost effectiveness due to high water demand of poplar species. High biomass productivity depends on optimal water supply. Also, numerous adaptations to water deficits result in an undesirable decrease of yield. Combined physiological and genetic investigations were conducted within a six-year old F1-full-sib crossbred population of European aspen (Populus tremula L., growing period 1998-2003). Possible implications on selection, breeding or improvement of poplar cultivars showing a high tolerance to water deficits are discussed. For the work presented here, the breeding goal of higher water deficit tolerance was defined as the minimisation of yield losses under dry conditions. Beyond growth related traits (aggregate yield (BM), aboveground woody biomass), biomass increment (iBM) and radial increment (ir), physiological and wood anatomical traits were included; these are related to reactions to water deficit and are measurable on tree rings retrospectively. These traits were the Carbon- and Oxygen isotope ratios (δ13C, δ18O), the fibre length and vessel element length (FL, GL), the vessel lumen cross sectional area (AG), the vessel density (GD), the cumulative vessel lumen area to cross sectional area ratio (LQ), the hydraulically weighted mean vessel lumen diameter (Dh) and wood density assessed by X-ray densitometry (RD). To distinguish the drought induced physiologic reactions from juvenile developmental patterns of the mapping population, juvenile trends of RD, FL, GL, and ir, which are representative of habitats in south-eastern Germany, were investigated in a second aspen collective that was selected from natural succession. During the first three years, the mapping population showed deviations from the juvenile trends due to water deficit adaptations or preferential root development, respectively. Due to drought in the growing seasons of 2000 and 2003, the juvenile trends show outstanding values for both years, although ground water supply in 2003 was exceptionally good following the intense rain event of 2002 (Elbe flood 2002). The tree ring traits of both years stand out from the juvenile trends due to drought adaptations. In 2000, all phenotypic traits showed a significant deviation from their respective trends. In 2003, only GL and RD showed an adaptation to drought as observable by a deviation from their juvenile trends. A significant decrease in water use efficiency (WUE) and an increase in net transpiration, respectively, were shown for 2003 by means of δ13C or δ18O values. All other traits showed an increase following their juvenile trends. RD data for 2000 and 2003 were not significantly correlated with BM, but δ13C data (and therefore WUE) for 2002 and 2003 revealed a weakly positive correlation with BM. The genotype that was most tolerant to water deficits showed a combination of a superior growth with a superior WUE (by means of δ13C), a superior AG, and an RD close to but not less than the population average. Due to the lack of negative correlation between BM and δ13C or BM and RD in the present work, δ13C and RD can be valuable proxies for the determination of drought tolerance of aspen trees for tree improvement purposes. Aside from BM under dry conditions, no other traits that were investigated can be recommended as a stand-alone proxy for water deficit tolerance. For a water deficit tolerance evaluation, pairs of traits should be used, of which one trait is positively correlated with yield and the other represents a water deficit adaptation. Both the primary breeding goal of the highest possible yield as well as a better water deficit tolerance should always be considered in this context. Two different drought tolerance indices were used to rank the individuals of the mapping population according to their water deficit tolerance. In both cases, trees with higher BM were ranked better. The second focus of the present work is on genetic mapping of Quantitative Trait Loci (QTL) for the investigated tree-ring traits that refer to water deficit reaction. As a basis for the QTL-mapping approach, genetic linkage maps were constructed for each parental tree of the F1-full-sib crossbred mapping-population following the two-way pseudo-testcross mapping strategy. The maternal map (P. tremula, “Schandau 4”) consisted of 157 markers (144 AFLP, 13 SSR) in 30 linkage groups and covered 1,369 cM. The 21 linkage groups of the paternal map (P. tremula, “Lichtenhain 1”) covered 1,079 cM of the genome (144 AFLP, 13 SSR). Compared with the haploid chromosome number (19) of the Populus genome, the high number of linkage groups, doublets and unlinked markers indicated low genome coverage. Only a low number of QTL was detected, maximal two per in¬vesti¬gated phenotypic trait with a relation to water deficit tolerance. One QTL having a pleiotropic effect on several growth related traits was detected on the maternal linkage group 1 (corresponding to the Populus Chromosome I). The significance of the QTL effects seemed to increase with tree age.

Holz aus Kurzumtriebsplantagen (KUP) mit Pappeln (Populus spp.) kann eine bedeutende Rolle im Mix der Bioenergieressourcen in Deutschland spielen. Trotz eines günstigen Energieinput-Energieoutput-Verhältnisses ist das Erreichen wirtschaftlich zufriedenstellender Ergebnisse mit KUP jedoch auf den meisten potenziellen Anbauflächen durch hohe Ansprüche der Pappeln an die Wasserversorgung erschwert. Hohe Produktivitätsraten der Pappeln sind an einen hohen Wasserverbrauch gebunden und viele Trockenheitsanpassungen führen zu deutlichen Ertragsrückgängen. In der vorgestellten Arbeit wurde eine sechsjährige Vollgeschwister-F1-Kartierungspopulation der Europäischen Zitter Pappel (Aspe, Populus tremula L., Wuchsperiode 1998-2003) physiologisch und genetisch untersucht, um mögliche Wege zu einer züchterischen Verbesserung der Trockenheitstoleranz von Pappeln diskutieren zu können. Dabei wurde das Zuchtziel der Trockenheitstoleranz als Minimierung der Ertragsrückgänge unter trockenen Bedingungen definiert. Neben wuchsleistungsbezogenen Größen (Biomassegesamtleistung (BM, oberirdische Dendromasse), Biomassezuwachs (iBM), Radialzuwachs (ir), Baumhöhe (h)) wurden physiologisch holzanatomische Eigenschaften untersucht, die retrospektiv anhand der Jahrringe messbar sind und zur nicht direkt messbaren Eigenschaft der Trockenheitstoleranz in einer Beziehung stehen. Diese waren die Kohlenstoff- und Sauerstoffisotopsignatur (δ13C, δ18O), die Faser- und Gefäßgliedlänge (FL, GL), die Gefäßlumenquerschnittsfläche (AG), die Gefäßdichte (GD), der potenziell Saftstrom leitende Querschnittsflächenanteil (LQ), der hydraulisch gewichtete Gefäßlumendurchmesser (Dh) und die röntgendensitometrische Holzdichte (RD). Um trockenheitsbedingte physiologische Reaktionen vom Einfluss der Juvenilität der Kartierungspopulation unterscheiden zu können, wurden regionaltypische Juvenilitätstrends der RD, FL, GL, und des ir anhand eines zweiten, für das östliche Deutschland repräsentativen Aspen-Kollektivs aus natürlicher Sukzession ermittelt. Bedingt durch Trockenheitsanpassungen bzw. eine bevorzugte Wurzelentwicklung nach dem Verpflanzen zeigte die Kartierungspopulation in den ersten drei Jahrringen Abweichungen von den regionaltypischen Juvenilitätstrends. In den Trendverläufen der Kartierungspopulation heben sich die beiden Trockenvegetationsperioden 2000 und 2003 ab, wobei bis zum Sommer 2003 infolge des Starkniederschlages 2002 (Flut) ein außergewöhnlich gutes Grundwasserangebot herrschte. Alle untersuchten phänotypischen Eigenschaften zeigten 2000 starke trockenheitsbedingte Abweichungen. Im Jahrring 2003 wichen nur die GL und die RD von ihren Juvenilitätstrends ab. Außerdem konnte anhand der δ13C und δ18O Werte eine signifikante Abnahme der Wassernutzungseffizienz bzw. eine Zunahme der Transpiration im Jahr 2003 gezeigt werden. Die übrigen Größen folgten ihren Juvenilitätstrends und stiegen an. Die Jahrringdatensätze 2000 und 2003 der RD waren nicht signifikant mit der BM korreliert, dagegen zeigten die δ13C Datensätze 2002 und 2003 schwach positive Korrelationen mit der BM. Der trockenheitstoleranteste Genotyp verband seine überdurchschnittliche BM mit einer hohen Wassernutzungseffizienz (angezeigt durch überdurchschnittliche δ13C Werte), mit einer überdurchschnittlichen AG und mit einer nicht unterdurchschnittlichen RD in Höhe des Populationsmittels. Aufgrund des Fehlens negativer Korrelationen zwischen BM und δ13C bzw. BM und RD in der vorliegenden Arbeit können δ13C und RD als nützliche Weiser für die Unterscheidung der Trockenheitstoleranz verschiedener Aspen zu züchterischen Zwecken vorgeschlagen werden. Außer der BM unter trockenen Bedingungen kann keine der untersuchten Eigenschaften als alleiniger Trockenheitstoleranzweiser empfohlen werden. Zu einer Trockenheitstoleranzbewertung sollten Merkmalspaare verwendet werden, von denen ein Merkmal positiv mit dem Ertrag korreliert ist und das andere eine Trockenheitsanpassung verkörpert. Dadurch werden sowohl das primäre Zuchtziel eines höchstmöglichen Ertrages als auch eine bessere Trockenheitsangepasstheit berücksichtigt. Zwei verschiedene Trockenheitstoleranzindizierungen wurden angewendet, um die Kartierungsnachkommen entsprechend ihrer Trockenheitstoleranz einem Ranking zu unterziehen. Dabei wurden in beiden Fällen Bäume mit einem höheren Ertrag besser platziert. Der zweite Schwerpunkt der Arbeit lag auf der genetischen Kartierung von Quantitative Trait Loci (QTL) für die untersuchten phänotypischen Jahrringeigenschaften mit Bezug zur Trockenheitstoleranz. Als Basis für das QTL Mapping wurden, der Pseudo-Testcross-Mapping-Strategie folgend, genetische Kopplungskarten für die Elternbäume der Kartierungspopulation konstruiert. Die maternale Karte (P. tremula, „Schandau 4“) deckte mit 157 Markern (144 AFLP, 13 SSR) in 30 Kopplungsgruppen 1.369 cM ab, die 21 paternalen Kopplungsgruppen mit 148 Markern (132 AFLP, 16 SSR) überspannten 1.079 cM des Genoms (P. tremula, „Lichtenhain 1“). Die im Vergleich zur haploiden Chromosomenzahl der Pappeln (19) hohen Zahlen an Kopplungsgruppen sowie die hohen Zahlen an Doublets und unkartierten Markern zeigten eine geringe Genomabdeckung an. So konnte nur eine begrenzte Zahl, höchstens zwei QTL für die untersuchten phänotypischen Jahrringeigenschaften mit Bezug zur Trockenheitstoleranz, kartiert werden. Ein QTL Bereich mit pleiotropem Effekt auf mehrere wachstumsbezogene Größen wurde auf der maternalen Kopplungsgruppe 1 (dem Populus Chromosom I zuzuordnen) detektiert. Die Signifikanz der Effekte dieses QTL auf den Radialzuwachs entwickelte sich steigend mit zunehmendem Baumalter. / Wood production in short rotation coppices (SRC) with poplar (Populus spp.) can contribute significantly to the future bio energy supply mix in Germany. Although the energy-input to energy-output ratio is rather good, SRC often do not meet cost effectiveness due to high water demand of poplar species. High biomass productivity depends on optimal water supply. Also, numerous adaptations to water deficits result in an undesirable decrease of yield. Combined physiological and genetic investigations were conducted within a six-year old F1-full-sib crossbred population of European aspen (Populus tremula L., growing period 1998-2003). Possible implications on selection, breeding or improvement of poplar cultivars showing a high tolerance to water deficits are discussed. For the work presented here, the breeding goal of higher water deficit tolerance was defined as the minimisation of yield losses under dry conditions. Beyond growth related traits (aggregate yield (BM), aboveground woody biomass), biomass increment (iBM) and radial increment (ir), physiological and wood anatomical traits were included; these are related to reactions to water deficit and are measurable on tree rings retrospectively. These traits were the Carbon- and Oxygen isotope ratios (δ13C, δ18O), the fibre length and vessel element length (FL, GL), the vessel lumen cross sectional area (AG), the vessel density (GD), the cumulative vessel lumen area to cross sectional area ratio (LQ), the hydraulically weighted mean vessel lumen diameter (Dh) and wood density assessed by X-ray densitometry (RD). To distinguish the drought induced physiologic reactions from juvenile developmental patterns of the mapping population, juvenile trends of RD, FL, GL, and ir, which are representative of habitats in south-eastern Germany, were investigated in a second aspen collective that was selected from natural succession. During the first three years, the mapping population showed deviations from the juvenile trends due to water deficit adaptations or preferential root development, respectively. Due to drought in the growing seasons of 2000 and 2003, the juvenile trends show outstanding values for both years, although ground water supply in 2003 was exceptionally good following the intense rain event of 2002 (Elbe flood 2002). The tree ring traits of both years stand out from the juvenile trends due to drought adaptations. In 2000, all phenotypic traits showed a significant deviation from their respective trends. In 2003, only GL and RD showed an adaptation to drought as observable by a deviation from their juvenile trends. A significant decrease in water use efficiency (WUE) and an increase in net transpiration, respectively, were shown for 2003 by means of δ13C or δ18O values. All other traits showed an increase following their juvenile trends. RD data for 2000 and 2003 were not significantly correlated with BM, but δ13C data (and therefore WUE) for 2002 and 2003 revealed a weakly positive correlation with BM. The genotype that was most tolerant to water deficits showed a combination of a superior growth with a superior WUE (by means of δ13C), a superior AG, and an RD close to but not less than the population average. Due to the lack of negative correlation between BM and δ13C or BM and RD in the present work, δ13C and RD can be valuable proxies for the determination of drought tolerance of aspen trees for tree improvement purposes. Aside from BM under dry conditions, no other traits that were investigated can be recommended as a stand-alone proxy for water deficit tolerance. For a water deficit tolerance evaluation, pairs of traits should be used, of which one trait is positively correlated with yield and the other represents a water deficit adaptation. Both the primary breeding goal of the highest possible yield as well as a better water deficit tolerance should always be considered in this context. Two different drought tolerance indices were used to rank the individuals of the mapping population according to their water deficit tolerance. In both cases, trees with higher BM were ranked better. The second focus of the present work is on genetic mapping of Quantitative Trait Loci (QTL) for the investigated tree-ring traits that refer to water deficit reaction. As a basis for the QTL-mapping approach, genetic linkage maps were constructed for each parental tree of the F1-full-sib crossbred mapping-population following the two-way pseudo-testcross mapping strategy. The maternal map (P. tremula, “Schandau 4”) consisted of 157 markers (144 AFLP, 13 SSR) in 30 linkage groups and covered 1,369 cM. The 21 linkage groups of the paternal map (P. tremula, “Lichtenhain 1”) covered 1,079 cM of the genome (144 AFLP, 13 SSR). Compared with the haploid chromosome number (19) of the Populus genome, the high number of linkage groups, doublets and unlinked markers indicated low genome coverage. Only a low number of QTL was detected, maximal two per in¬vesti¬gated phenotypic trait with a relation to water deficit tolerance. One QTL having a pleiotropic effect on several growth related traits was detected on the maternal linkage group 1 (corresponding to the Populus Chromosome I). The significance of the QTL effects seemed to increase with tree age.