Mice carrying a targeted mutation in their Adam22 gene were generated by homologous recombination (Fig. 1A). Correct targeting events were confirmed by Southern blot analysis (Fig. 1B). Since the termination codon was introduced in exon 8 in the pro-protein domain, only the truncated form of the ADAM22 protein would be synthesized from this targeted allele. Because a pro-protein domain is always removed in the mature functional ADAM-proteins by the Furin-like proteases and is thought to be non-functional itself, we considered that this truncated form of ADAM22 protein has no function. Absence of mature ADAM22 protein in homozygous mutants was confirmed by Western blot analysis using the specific antibody, which recognizes the cytoplasmic domain of the ADAM22 protein (Fig. 1C). Homozygous mutants showed no noticeable defects at birth and were indistinguishable from wild-type or heterozygous littermates during the first week. At postnatal day 10 (P10), most of the homozygous mutants were distinguishable by abnormalities such as reduced body weight and uncoordinated movements of their limbs. After P10, all homozygotes displayed severe ataxia (Fig. 2) and began to die. To measure the survival rate and body weight of each genotype precisely, we backcrossed heterozygous male mutants to C57BL/6 females more than 6 times. The resulting (N 6) heterozygous males and females were intercrossed and the produced offspring were analysed. The numbers of survivors of each genotype every 5 days are shown in Table 1. At P10, the ratio of each genotype was in close accordance with the Mendelian ratio (20.5% +/+, 55.1% +/-, 24.4% -/- ; n = 78). This result shows that ADAM22 is not essential for embryogenesis. At P10, the average body weight of homozygous mutants was approximately half that of wild-type and heterozygous littermates (Table 2). Homozygous mutants died one by one after P10, and all homozygotes died before P20. Of more than 100 homozygotes we have produced, none have survived more than 25 days after birth. Meanwhile, heterozygous mutants looked normal, were fertile, and survived for more than one year without obvious defects.