In a Ts65Dn mouse model of DS, it was demonstrated that the amyloid precursor protein (APP) triplicated gene impairs proliferation of NPCs from SVZ in the hippocampus [85,86] because high levels of the intracellular domain from APP cleavage by γ-secretase can raise the transcription of Ptch1, which is known to repress Shh pathway [85,86]. The gene discussed is SHH; the disease is Dravet syndrome.