Mating of mice heterozygous for the ADAM11 mutation yielded a near-Mendelian distribution of genotypes in the offspring and the ratio of females and males was the same in all groups (data not shown). For the present experiments, ADAM11-deficient male mice (backcrossed generations into C57BL/6NCrj, n = 14) were used in all behavioural analyses and anatomical-histological studies. Homozygous ADAM11-deficient mice were viable and appeared normal, indicating that the Adam11 gene is not essential to development and survival. The gain in body weight of (-/-) mice was comparable to that of (+/+) and (+/-) mice at least until 24 weeks of age (data not shown). There was no significant difference in locomotor activity among (+/+), (+/-) and (-/-) genotypes (data not shown). No apparent anatomical-histological change was observed in the spinal cord, heart, lung, liver, kidney, spleen, testis or ovary (data not shown). The brain of (-/-) mice, including the hippocampus (Fig. 1D) and cerebellum (Fig. 1E) appeared normal after HE staining when (+/+), (+/-) and (-/-) mice were compared. Since Adam11 is predominantly expressed in the hippocampus and cerebellum, we applied hippocampus- or cerebellum-dependent behavioural analyses.