The phenotypes of three mouse strains that carry the acetylcholinesterase knockout (AChE KO) mutation have been compared. The AChE KO mouse was developed from embryonic stem (ES) cells, originating from a 129/Sv blastocyst. Animals generated from strain 129/Sv suffer from dysgenesis of the corpus callosum and possibly a number of other neuroanatomical deficiencies. To determine the contribution of background genes to phenotype, 129/Sv AChE heterozygote (AChE+/-) mice were backcrossed 10 generations with wild-type inbred C57/BL6 (C57) mice and with wild-type outbred CD1(R) mice. AChE-/- mice in strains C57 and CD1died during seizures before postnatal day (P) 21, whereas mice in strain 129/Sv lived to adulthood.