Le Syndrome de Down ou trisomie 21 est une maladie congénitale complexe qui affecte le développement du système nerveux ainsi que de nombreuses autres fonctions. Ce syndrome résulte de la présence en trois copies de tout ou partie du chromosome 21. Plusieurs modèles murins existent et ont été largement étudiés, mais tous ne reproduisent pas la totalité du phénotype observé chez l’homme. Au sein de notre laboratoire, nous avons créé un modèle qui porte la délétion et la duplication de la région télomérique du HS2A21, localisée sur le MMU10. Avec le modèle comprenant la délétion nous avons réalisé une expérience de sauvetage de phénotype visant à réduire le nombre de copie fonctionnelle des gènes de cette région (Prmt2-Cstb) dans le modèle trans-chromosomique Tc1 (O’Doherty et al. 2005). La lignée Tc1 est un modèle de souris trisomiques pour l’ensemble des gènes homologues du chromosome 21. Elle présente un ensemble d’altérations morphologiques, comportementales et physiologiques similaires aux défauts observés chez les patients. Les résultats que nous avons obtenus montrent la robustesse du modèle TC1, puisque les phénotypes caractérisés ont été retrouvés dans nos expériences, malgré l’utilisation d’un fond génétique différent de celui d’origine. Cependant, nous n’avons pas obtenus de sauvetage de phénotypes dans les tests que nous avons réalisés en réduisant le nombre de copie de la région Cstb-Prmt2 dans ce modèle trisomique. Ces résultats tendent à montrer que cette région ne jouerait pas de rôle majeur dans les phénotypes du Syndrome de Down et permet de réduire les régions et gènes incriminés dans cette pathologie. / The Down syndrome or trisomy 21 is a complexe congenital disease, neuro-degenerative, which affects the embryonic development. It’s the most frequent human aneuploïdy and the leading cause of backwardness. This syndrome results from the presence in three copies of whole or part of chromosome 21. Within our laboratory, we created a model which carries the deletion and duplication of the telomeric part of the HS2A21, located on the MMU10. With this model, we carried out an experiment of phenotype rescue, by reducing the number of functional copy of genes in this region (Prmt2-Cstb) in the trans-chromosomal model Tc1 (O' Doherty et al. 2005). The Tc1 line is a model of trisomic mice for the whole of chromosome 21 genes. It presents a set of morphological, behavioral and physiological alterations similar to the defects observed among patients. To isolate the possible specific gene-phenotypes relations, the Tc1 line was examined in the Tc1- Ms4Yah context, in a phenotypical screening composed of learning, cognitive and motor tests. The results obtained do not show phenotypes rescue in the tests which we carried out by reducing the number of copy of the Cstb-Prmt2 region in this trisomic model. These results tend to show that this region would not play of important role in the Down syndrome phenotypes and makes it possible to reduce the genes implicated in this pathology.

The Arabidopsis chitinase-like1 (Atctl1) mutant, pom1 is compromised in primary cell wall development, resulting in short roots when grown on high sucrose and shortened hypocotyls when grown in darkness. To better understand this phenotype and the evolution of AtCTL1 and its homologue, AtCTL2, we obtained a large number of CTL sequences and determined the phylogenetic relationships among them. Since microarray analysis had suggested a change in auxin response or homeostasis in pom1, I used the auxin reporter DR5::GUS in the pom1 background to assess changes in distribution. To assess whether the biochemical functions of AtCTL1 homologues in Arabidopsis and other plants are conserved, I transformed pom1 with AtCTL2 and CTLs from poplar (Populus trichocarpa x Populus deltoides clone H-11) and from Picea glauca (spruce) and assessed rescue of the pom1 phenotype. To further understand CTL expression and function, Arabidopsis and poplar CTL promoter::GUS fusions were also expressed in Arabidopsis, PopCTL1 overexpressed in Arabidopsis, and CTL expression down regulated in poplar by RNAi. Our results indicate that CTL genes represent an ancient family encoding proteins of conserved biochemical function. In dicots, represented by Arabidopsis and poplar) duplicated CTL genes are differentially expressed in conjunction with primary and secondary cell wall development, respectively. Mutation of these genes results in improperly formed primary walls in certain cell types in the case of AtCTL1, and an impairment in the differentiation of vascular bundles for AtCTL2. Overexpression of PopCTL1 in Arabidopsis seems to over stimulate the differentiation of vascular bundles, and our studies show that auxin distribution is altered in the Atctl1 mutant. Down regulation of PopCTL1 and PopCTL2 in poplar appears to phenocopy aspects of these mutations, resulting in secondary cell walls that appear to have less deposition of lignin and an accelerated production of secondary xylem respectively. While specific biochemical function(s) of CTL genes were not studied, potential functions are discussed.

The Arabidopsis chitinase-like1 (Atctl1) mutant, pom1 is compromised in primary cell wall development, resulting in short roots when grown on high sucrose and shortened hypocotyls when grown in darkness. To better understand this phenotype and the evolution of AtCTL1 and its homologue, AtCTL2, we obtained a large number of CTL sequences and determined the phylogenetic relationships among them. Since microarray analysis had suggested a change in auxin response or homeostasis in pom1, I used the auxin reporter DR5::GUS in the pom1 background to assess changes in distribution. To assess whether the biochemical functions of AtCTL1 homologues in Arabidopsis and other plants are conserved, I transformed pom1 with AtCTL2 and CTLs from poplar (Populus trichocarpa x Populus deltoides clone H-11) and from Picea glauca (spruce) and assessed rescue of the pom1 phenotype. To further understand CTL expression and function, Arabidopsis and poplar CTL promoter::GUS fusions were also expressed in Arabidopsis, PopCTL1 overexpressed in Arabidopsis, and CTL expression down regulated in poplar by RNAi. Our results indicate that CTL genes represent an ancient family encoding proteins of conserved biochemical function. In dicots, represented by Arabidopsis and poplar) duplicated CTL genes are differentially expressed in conjunction with primary and secondary cell wall development, respectively. Mutation of these genes results in improperly formed primary walls in certain cell types in the case of AtCTL1, and an impairment in the differentiation of vascular bundles for AtCTL2. Overexpression of PopCTL1 in Arabidopsis seems to over stimulate the differentiation of vascular bundles, and our studies show that auxin distribution is altered in the Atctl1 mutant. Down regulation of PopCTL1 and PopCTL2 in poplar appears to phenocopy aspects of these mutations, resulting in secondary cell walls that appear to have less deposition of lignin and an accelerated production of secondary xylem respectively. While specific biochemical function(s) of CTL genes were not studied, potential functions are discussed.