THE BONE MORPHOGENETIC PROTEIN-15 GENE IS X-LINKED AND EXPRESSED IN OOCYTES

We have taken advantage of the sequence relationships among the bone m orphogenetic proteins (BMPs) to identify the mouse Bmp15 and human BMP 15 genes. The 392-amino acid prepropeptides encoded by these BMP genes exhibit significant homology to each other, although the 70% identity observed between the 125-amino acid mature peptides is considerably l ower than that seen in comparisons of other mouse and human orthologs. Both genes share a common structural organization and encode mature p eptides that lack the cysteine residue normally involved in the format ion of a covalent dimer. In addition, mouse Bmp15 and human BMP15 map to conserved syntenic regions on the X chromosome. We demonstrate, thr ough a combination of Northern blot and in situ hybridization analyses , that mouse Bmp15 is expressed specifically in the oocyte beginning a t the one-layer primary follicle stage and continuing through ovulatio n. Interestingly, BMP-15 is most closely related to and shares a coinc ident expression pattern with the mouse growth/differentiation factor 9 (GDF-9) gene that is essential for female fertility. Our findings wi ll be important for defining the role of BMP-15 in follicular developm ent.