To assess the contribution of the DS phenotype associated with the 9.4 Mb Hspa13-App Hsa21 syntenic region on Mmu16 that is not trisomic in the widely used Ts65Dn model, we generated through chromosome engineering a trisomic mouse model (Ts3Yah) and the corresponding monosomic model (Ms3Yah) for this region. Here, HSPA13 is linked to Dravet syndrome.