Spelling suggestions: "subject:"mice -- genetics"" "subject:"mice -- kenetics""
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Dissecting the genetics of complex trait in mouse: an attempt using public resources and in-houseknockoutTang, Ling-fung, Paul, 鄧凌鋒 January 2010 (has links)
published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy
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Characterization of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced modification of hepatic pyruvate carboxylase gene expression in C57BL/6J male miceSparrow, Barney R. 08 April 1997 (has links)
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on hepatic
pyruvate carboxylase (PC) gene expression were investigated in C57BL/6J Ah[superscipt b/b male
mice. A dose-dependent reduction of PC levels and activity occurred in animals given a
single intraperitoneal dose of TCDD in a corn oil carrier. The dose ranged from 1 to
75 ug/kg body weight and the analysis performed 8 days postinjection. At the
maximum TCDD level investigated, a 10-fold reduction in PC activity occurred. At
doses beyond those required to initiate a reduction in PC, a lactate dehydrogenase
isozyme patterns shift is observed. This is accompanied by increases in blood lactic
acid levels. Northern blot analysis on RNA extracts from hepatic tissues indicated that
at 8 days post TCDD treatment, a dose-dependent reduction of hepatic mRNA levels
occurs.
The aryl hydrocarbon receptor (AhR) is believed to mediate all responses to
TCDD. Liganded AhR and the aryl hydrocarbon receptor nuclear translocator (ARNT)
protein form a heterodimeric transcription factor which interacts with dioxin response
elements (DREs). These are found in enhancer/promoter regions of many genes that
respond transcriptionally to TCDD exposure. Cloning and sequencing a region
approximately 1.4 kb upstream of the PC translational start site revealed an untranslated
leader sequence of 124 nucleotides starting with adenosine. Primary structural analysis
of the upstream region revealed an 1nr element in place of a TATA element. Additional
transcription factor elements were identified including: Spl, GCF, UBP-1, GRE, CREB,
NF-1, HNF-4, TFII-I and E-boxes; DRE elements were notably lacking. A tandem
series of 10 evenly spaced E-boxes, which bind ARNT homodimers, are each
juxtaposed to a TFII-I element, possibly forming composite elements. Tertiary structure
analysis revealed the positioning of nine composite elements displayed as a trio of
phased elements.
Transient transfections into Hepa lc1c7 cells, using a luciferase reporter gene
under the transcriptional control of the PC upstream region, unlike the animal studies,
produced an induction in activity in the presence of 10 nM TCDD. Co-transfections
with an ARNT encoding plasmid reduced induction indicating overexpression of ARNT
protein partially overrides the TCDD-induced increase in activity. These results in
relationship to whole animal experiments are discussed. / Graduation date: 1997
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Analysis of lacZ gene expression patterns of a Hoxb3[lacZ] mouse mutant during early developmentCheung, Kwan-lok., 張君樂. January 2005 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
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Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies in miceKam, Ka-man., 甘嘉敏. January 2011 (has links)
Neural crest cells (NCC) arise from the neural tube (NT) and migrate through given regions of embryos, where they generate most of the peripheral nervous system (PNS), facial skeleton and pigment cells. Defective NCC development gives rises to malformations in multiple NCC-derived structures, collectively known as neurocristopathies.
NCC from the NT vagal and trunk levels express Hoxb5 plus a number of other Hox proteins. Hoxb5 is a member of Hox transcription factors family that binds to specific target nucleotide sequences in the genome via their DNA-binding domain, where they regulate gene expressions. Vagal NCC migrate to the intestine and generate the enteric nervous system (ENS). To test the Hoxb5 function in vagal NCC, we made use a transgenic mouse line (enb5) and showed that perturbation of Hoxb5 signaling in NCC resulted in down-regulation of Ret and defective ENS, indicating that normal Hoxb5 function was required for the development of vagal NCC.
Current project aims to investigate the function of Hoxb5 in trunk NCC development. Transgenic mouse enb5 can be induced by Cre recombinase to express a hybrid protein namely engrailed-Hoxb5 (enb5), in which the transactivation domain of the mouse Hoxb5 is replaced with a repressor domain of the Drosophila engrailed (en) protein. With the intact DNA-binding domain, enb5 binds to target genes of Hoxb5, repressing the expression of target genes instead of induction. Therefore, enb5 produces a dominant negative effect on the developmental pathways that normally require Hoxb5. In this study, enb5 mice were crossed to Wnt1-Cre mice to express enb5 in NCC that arose from the entire length of NT. Wnt1-Cre/enb5 mutants displayed apoptosis of NCC, skin hypopigmentation and PNS defects (hypoplastic dorsal root ganglion and defective ENS). Expression of Sox9, Foxd3 and Ret was down-regulated in Wnt1-Cre/enb5 embryos. Conditional deletion of Sox9 and Foxd3 by Wnt1-Cre, or conventional deletion of Ret in mice produced NCC phenoptypes similar to those of Wnt1-Cre/enb5. Taken all these prompted me to further investigate if Hoxb5 functioned in the same pathway as Sox9 and Foxd3 for NCC development using multiple experimental approaches.
In ovo electroporation of enb5 in chick embryos induced apoptosis of NT, and co-electroporation of Hoxb5, Ret, Sox9 or Foxd3 rescued enb5-induced cell death. By bioinformatics analysis, Hoxb5 binding sites were identified in SOX9 and FOXD3 promoter sequences. Binding of Hoxb5 protein onto these binding sites of SOX9 and FOXD3 promoters was revealed by electro-mobility shift assay and further confirmed by chromatin immuno-precipitation assay. In addition, enb5 was also shown to bind to the same regions of SOX9 and FOXD3 promoters as Hoxb5. Using dual luciferase reporter assay, Hoxb5 was shown to induce transcription from SOX9 and FOXD3 promoters, and enb5 blocked the induction. Taken all these indicate that (i) Hoxb5 binds and induces transcriptions from SOX9 and FOXD3 promoters, (ii) enb5 blocks the induction. In summary, Hoxb5 regulates NCC development by controlling the expression of Sox9, Foxd3 and Ret, and perturbation of Hoxb5 signaling results in NCC death and neurocristopathies. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy
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Analysis of abnormal phenotypes of Hoxb3 mouse mutants generated by gene targetingWong, Kung-yen, Corinne., 黃共欣. January 2003 (has links)
published_or_final_version / abstract / toc / Biochemistry / Master / Master of Philosophy
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Generation and analysis of transgenic mice expressing collagen X with a mutation in the NC1 domainHo, Sai-pong., 何世邦 January 2002 (has links)
published_or_final_version / Biochemistry / Master / Master of Philosophy
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Molecular cloning and characterization of mouse testin complementary DNA張朝雄, Cheung, Chiu-hung. January 1999 (has links)
published_or_final_version / Zoology / Master / Master of Philosophy
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Analysis of transgenic mice with ectopic Hoxb-3 expression in rhombomere 4麥小珊, Mak, Siu-shan, Suzanne. January 2000 (has links)
published_or_final_version / Biochemistry / Master / Master of Philosophy
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Studies of the regulation of mouse Hoxb-3 gene關仲天, Kwan, Chung-tin. January 1998 (has links)
published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy
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Collagen gene expression in embryonic stem cells and in mouse development劉嚴德光, Lau Yim, Tak-kwong, Elizabeth. January 1991 (has links)
published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy
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