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sksis a mutant mouse strain showing sterility in both males and females caused by defects of gametogenesis. They also show skeletal malformations caused by fusion of vertebrae and ribs. The locus responsible for these phenotypes has been mapped on mouse chromosome 4. In this study, we identified the causative gene for the sksmutant by positional cloning, which is expected to play an important role in gametogenesis and embryonic development of mammals. Histological examination and RT-PCR of the marker genes specifically expressed in particular stages of spermatogenesis confirmed that the sksmutant mice showed arrest of spermatogenesis at the pachytene stage of the prophase of meiosis and the spermatogenesis does not proceed beyond this stage. Immunofluorescence staining using anti-SCP3 antibody and anti-gamma- H2AX antibody revealed impaired synapsis of homologous chromosomes in pachytene spermatocyte. These findings suggested that the gene responsible for the sksmutant play an essential role in a progression of meiosis during prophase. To find the gene responsible for these phenotypes, we performed a linkage analysis using the F2progeny consisting of 63 affected and 469 normal mice and refined the chromosomal localization of the skslocus in 0.6-Mb interval of mouse chromosome 4. This region contained 13 genes including ESTs and predicted genes with unknown functions. Sequence analysis of these genes revealed GG to TT nucleotide substitution in coding region of Tmem48gene, which encodes a putative transmembrane protein with several transmembrane domains. The nucleotide substitution resulted in aberrant splicing of the gene causing a deletion of one exon in Tmem48transcripts. Tmem48 has also been named NDC1 in human, which is a nuclear membrane protein involving in the nuclear pore assembly. Since nuclear membrane has important role in paring of homologous chromosomes during meiotic prophase, Tmem48/Ndc1 expected to be involved in the pairing of homologous chromosomes during prophase of meiosis controlled by nuclear membrane. in situhybridization of mouse testis showed strong expression of Tmem48/Ndc1 in spermatogonia and spermatocytes but no expression was observed in spermatids. We concluded that the nucleotide substitution of the Tmem48/Ndc1gene is responsible for the arrest of spermatogenesis in the sksmice and Tmem48/Ndc1 play an important role in the mammalian gametogenesis. (poster)