Dendritic phenotype and proliferation potency in the hippocampal dentate gyrus of the Ts66Yah model of Down syndrome

The Ts65Dn mouse is the most widely used model of Down syndrome (DS), although, in addition to the triplication of 90 genes homologous to Human Chromosome 21 (Hsa21) genes, it bears the triplication of 46 extra genes. To clarify the latter’s impact, the Ts66Yah model has been created from the Ts65Dn mouse by exploiting CRISPR/Cas9 technology for extra gene deletion. It has been found that, similar to the Ts65Dn model, the Ts66Yah model exhibits impairment in hippocampus-dependent learning and memory and age-related hippocampal deterioration, with no increased activity. We examine here the dendritic development of the hippocampal granule neurons and the proliferation potency of granule cell precursors in Ts66Yah mice because these phenotypes are impaired in Ts65Dn mice and individuals with DS starting from early life stages and are thought to underpin cognitive impairment. In Ts66Yah mice aged 15 days and those aged three months, we found no reduction in dendritic arborization, dendritic spine density, proliferation potency, or total number of granule cells, suggesting that other mechanisms may underpin the behavioral impairment found in the Ts66Yah model in adulthood. Thus, the Ts66Yah model is unsuitable to study these neurodevelopmental alterations, although it may be useful to study other DS-related phenotypes.