BONE MORPHOGENETIC PROTEIN-8A PLAYS A ROLE IN THE MAINTENANCE OF SPERMATOGENESIS AND THE INTEGRITY OF THE EPIDIDYMIS

The murine Bmp8a and Bmp8b genes are tightly linked on mouse chromosom e 4 and have similar expression during reproduction. Previous studies have shown that targeted mutagenesis of Bmp8b causes male infertility due to germ cell degeneration. To investigate the function of Bmp8a, w e have inactivated the gene by homologous recombination. Heterozygous and homozygous Bmp8a mutants reveal normal embryonic and postnatal dev elopment. Despite high levels of Bmp8a expression in the deciduum, hom ozygous mutant females have normal fertility, suggesting that the gene is not essential for female reproduction. Bmp8a and Bmp8b are express ed in similar patterns in male germ cells. Unlike homozygous Bmp8b(tm1 ) mutants, homozygous Bmp8d(tm1) males do not show obvious germ cell d efects during the initiation of spermatogenesis. However, germ cell de generation is observed in 37% of adult homozygous Bmp8a(tm1) males, es tablishing a role of Bmp8a in the maintenance of spermatogenesis. A sm all proportion of the mating homozygous Bmp8d(tm1) males also show deg eneration of the epididymal epithelium, indicating a novel role for BM Ps in the control of epididymal function.