THE GENE ENCODING BONE MORPHOGENETIC PROTEIN 8B IS REQUIRED FOR THE INITIATION AND MAINTENANCE OF SPERMATOGENESIS IN THE MOUSE

Bone morphogenetic protein 8B (BMPBB) is a member of the TGF beta supe rfamily of growth factors. In the mouse, Bmp8b is expressed in male ge rm cells of the testis and trophoblast cells of the placenta, suggesti ng that it has a role in spermatogenesis and reproduction. To investig ate these possibilities, we have generated mice with a targeted mutati on in Bmp8b. Here, we show that homozygous Bmp8b(tm1blh) mutant males exhibit variable degrees of germ-cell deficiency and infertility. Deta iled analysis reveals two separable defects in the homozygous mutant t estes. First, during early puberty (2 weeks old or younger) the germ c ells of all homozygous mutants either fail to proliferate or show a ma rked reduction in proliferation and a delayed differentiation. Second, in adults, there is a significant increase in programmed cell death ( apoptosis) of spermatocytes, leading to germ-cell depletion and steril ity. Sertoli cells and Leydig cells appear relatively unaffected in mu tants. This study therefore provides the first genetic evidence that a murine germ cell-produced factor, BMP8B, is required for the resumpti on of male germ-cell proliferation in early puberty, and for germ-cell survival and fertility in the adult.