International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 102 - DEVELOPMENT OF NEW MODELS FOR THE DOWN SYNDROME BY CHROMOSOMAL ENGINEERING IN THE MICE

Levavasseur F
CNRS, Institut de transgenose, Orléans, France

Co-Authors: Besson V, Brault V, Duchon A, Labbe M, Luo F, Magnol L, Herault Y
Institutions: CNRS, Institut de transgenose, Orléans, France

Trisomy 21 (Down Syndrome) is one of the most common chromosomal disorders, occurring once in every 700 newborns. Down syndrome is a complex disorder, affecting the morphology and physiology of numerous organs, like the nervous system, heart, skeleton and gastrointestinal tract. It is due to dosage imbalance for genes carried by chromosome 21(HSA21). The murine homologues of HSA21 genes have been located in syntenic region on chromosomes 10 (MMU10); 16 (MMU16); 17 (MMU17). Several trisomic models have been produced in the mice and correspond to a partial or complete trisomy of MMU16. However, the most commonly used models display some features of the human syndrome including some behavioral phenotypes, but it does not resume the whole phenotype that should be expected. More animal models are required to get a better understanding of the molecular pathophysiology of the trisomy. Thus we have undertaken the creation of new mouse models carrying duplication of the homologous HSA21 regions on MMU10, MMU16 and MMU17. For this purpose, we are using the Cre-loxP-based chromosome engineering technology, combined with either the in vitro Hprt selection system or the in vivo TAMERE approach. Here, we will present the strategies developed as well as preliminary results concerning the region A on MMU16.


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