We report here that Ehmt1+/−, Ehmt1+/−/Ehmt2+/−and Mbd5+/− mice show hypoactivity and learning and memory deficits in several situations, extending previously reported data in Ehmt1+/−mice [72,91], and recapitulating several cognitive, autistic and hypoactivity features observed in Kleefstra syndrome and 2q23.1 deletion patients, supporting the use of Ehmt1+/− and Mbd5+/− as good mammalian models for Kleefstra and Autosomal Dominant Mental Retardation 1/2q23.1 deletion syndromes. The gene discussed is EHMT1; the disease is Kleefstra syndrome.