| First Author | Herault Y | Year | 2009 |
| Pages | Abstr | Mgi Jnum | J:202375 |
| Mgi Id | MGI:5518847 | Citation | Herault Y, et al. (2009) Tackling the complexity of the genotype-phenotype relationship in the Down syndrome with the mouse aneuploidy zoo: a resource of new models to study aneuploidies involving human chromosome 21. :Abstr |
| abstractText | 50 Years after the discovery of the Trisomy 21, the underlying genetic basic of the Down syndrome (DS), the study of the complex genotypes - phenotypes relationship in DS is still a challenge. Currently it is accepted that interactions between "dosage sensitive" genes along the HSA21 are responsible for the complex feature of the pathology. Orthologues of genes on HSA21 exist in the same order separated on mouse chromosomes (MMU) 16, 17 and 10. Most of the exisiting mouse models for DS are trisomic for part of the MMU16 homologous region. These models exhibit many of the characteristics of DS, but not all the mechanisms have been described up to now. In order to complement these models and to decipher the gene interactions generating the DS phenotype, we created new partial trisomies and monosomies for different regions on MMU10, 16 and 17 that are homologous to HSA21 by using chromosomal engineering technic. Now we succeeded in getting a complete series of mouse trisomic models and monosomic models covering the region of the mouse genome homologous to HSA21. These models are listed below: New segmental trisomy, Chr., Modification (interval); Ts1Yah, MMU17, Dup(Abcg1-U2af1); Ts2Yah, MMU16, Dup(Stch-App); Ts3Yah, MMU10, Dup(Cstb-Prmt2); New Segmental Monosomy, Chr., Modification (interval); Ms1Yah, MMU10, Del(Col6a1-Prmt2); Ms2Yah, MMU17, Del(Abcg1-U2af1); Ms3Yah, MMU16, Del(Stch-App); Ms4Yah, MMU10, Del(Cstb-Prmt2); Ms5Yah, MMU16, Del(App-Runx1); Ms6Yah, MMU16, Del(Stch-Runx1); Using such a series we are now oriented toward deciphering the role of each region in the induction of DS phenotypes, their interactions and at term the signal pathways that are affected, with the hope that this would lead to development of new therapeutical approaches. We will report here the phenotypic analysis of the new models and the results obtained on cognition, learning and memory and gene expression in brain of such models. Then we will propose hypothesis to explain the physiopathology of the disease showing that genetic interactions can balance both negative and positive contributions, highlighting the complexity of the genetic codes in DS. |
