TESTICULAR DEGENERATION IN BCLW-DEFICIENT MICE

To identify genes required for mammalian spermatogenesis, we screened lines of mutant mice created using a retroviral gene-trap system(1) fo r male infertility. Homozygous ROSA41 male mice exhibit sterility asso ciated with progressive testicular degeneration. Germ-cell defects are first observed at 19 clays post-natal (p19). Spermatogenesis is block ed during late spermiogenesis in young adults. Gradual depletion of al l stages of germ cells results in a Sertoli-cell-only phenotype by app roximately six months of age. Subsequently, almost all Sertoli cells a re lost from the seminiferous tubules and the Leydig cell population i s reduced. Molecular analysis indicates that the gene mutated is Bclw, a death-protecting member of the Bcl2 family, The mutant allele of Bc lw in ROSA41 does not produce a Bclw polypeptide. Expression of Bclw i n the testis appears to be restricted to elongating spermatids and Ser toli cells. Potential roles for Bclw in testicular function are discus sed.