To determine if genes other than CSTB on Hsa21 when in three copies might be sufficient to modulate the activity of cathepsin B in mouse brain, we measured activity in the cortex of 3-month of age Dp1Tyb mouse model of DS, which has an additional copy of 148 Hsa21 homologous genes, including App, located on Mmu16 and the Dp(17)3Yey mouse model of DS, which has an additional copy of 17 Hsa21 homologues located on Mmu17. The gene discussed is APP; the disease is Dravet syndrome.