Mouse case

Summary The retina of Down syndrome ( DS ) patients is thicker than the one from controls, an anomaly reproduced in two murine models of the disease, Ts65Dn and Tg( Dyrk1a ) and attributed to the increased dosage of Dyrk1a (Laguna et al . 2013), considered as one of the key genes in the apparition of DS symptoms. As HSA 21 genes not triplicated in Ts65Dn may affect the expression/function of DYRK 1A, we have analyzed by optical coherence tomography ( OCT ) the retina of Ts65Dn and Tg( Dyrk1a ) mice, and compared the results to those obtained on various additional models, notably Dp(16)1 Yeh mice, which have a triplicated segment of MMU 16 longer than Ts65Dn, and crosses between Tg( Dyrk1a ) and Dp1 Yah, which carries a triplication of the MMU 17 genes orthologue to HSA 21. In parallel, we have started to analyze by immunohistochemistry the retinal neuron populations in Tg( Dyrk1a ) mice, showing an increase in dopaminergic amacrine cells when Dyrk1a is triplicated. Mirror results were obtained on the retina of Dyrk1a +/‐ , a model of Mental Retardation 7. Laguna et al . (2013 ): Triplication of DYRK 1A causes retinal structural and functional alterations in Down syndrome. Hum Mol Genet 15;22(14):2775‐84.