Estudio del efecto de la reducción del número de copias del gen Dyrk1A sobre distintos fenotipos funcionales y neuromorfológicos encontrados en un modelo murino de Síndrome de Down y en ratones euploides

Abstract

Down syndrome phenotypes are thought to result from overexpression of a number of dosage-sensitive genes. One of the genes that have been proposed to play a role in Down syndrome cognitive disabilities is DYRK1A. One of the mechanisms responsible for these learning and memory deficits is the hypocellularity found in different areas of their central nervous system due to altered neurogenesis. The Ts65Dn mouse, the most commonly used mouse model of Down syndrome, carries a partial trisomy a segment of Mmu16 including the Dyrk1A gene. Because Dyrk1A plays a role in neuronal progenitor proliferation and neurodifferentiation, in this study we evaluated whether normalization of Dyrk1A copy number in the Ts65Dn mouse could rescue some of their neuromorphological, electrophysiological and cognitive alterations. In addition, in order to characterize the physiological role of Dyrk1A gene, we also studied different phenotypes in euploid animals carrying a single copy of this gene