Partenaires et organisations internationales
(Anglais)
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Cancer Research Institute, Barcelona (E), Nicole Creau (CNRS1335), Paris (F), Jean M Delabar (CNRS1335) Paris (F), Jackeline London (CNRS1335), Paris (F), Marie-Laure Yaspo, Hans Lehrach (Max Plank) Berlin (D), Yoram Groner, Ditsa Levanon (Weizmann Institute of Science, Rehovot, (Israel), P Roubertoux (CNRS 9074), Paris (F), Jesus Flores, University of Cantabria (E)
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Résumé des résultats (Abstract)
(Anglais)
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Down syndrome, due to Trisomy 21 is the most common known cause of mental retardation. The nucleotide sequence of the long arm of chromosome 21 has now been completed and our laboratory has substantially contributed to this achievement. The 33.5 Mb sequence revealed approximately 240 genes, some of which may contribute to the various phenotypes of Down syndrome. The use of mouse models are necessary for the elucidation of the pathophysiology of this disorder. The human chromosome 21 sequences show homologies to portions of mouse chromosomes 16, 17 and 10. We have used single-gene transgenesis to evaluate the contribution of the SIM2 gene in the pathogenesis of DS. Trisomic SIM2 mice showed abnormalities in nociception, spacial exploration and social behaviour. Thus triplication of the SIM2 transcription factor may contribute to DS. In addition, we are developing in collaboration with Y. Herault mice trisomic for the HC21 syntenic region of murine chr 17 and chr 10 in order to achieve a mouse model that has triplication of all syntenic HC21 material (by performing appropriate crosses with the existing partial trisomy 16 mice).Finally, in order to test the hypothesis there is a global dysregulation of gene expression we studied the transcription of the brains of partial trisomy 16 mice versus normal litermates.The completion of the sequence of the mouse genome now provides new opportunities of the use of this animal model to elucidate the pathogenetic mechanisms of complex phenotypes such as Down syndrome.
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