Structure and sequence of the mouse Bmp6 gene

Inactivation of the Bmp5 and Bmp7 genes has provided preliminary insights into the developmental role of these proteins, with distinctive phenotypes of the mutant mice. We have begun to characterize the function of BMP-6 as a prototype factor of this subgroup. This cDNA was originally isolated from a murine embryonic cDNA library by screening under low stringency with a Xenopus vg-1 cDNA probe, and the corresponding protein was named Vgr-1. cDNAs for the human and bovine homologs of Vgr-1 were subsequently isolated and were named BMP-6, although no bone morphogenetic activity was originally reported for this protein. Extensive in situ hybridization and immunohistochemical analyses have localized BMP-6 mRNA and protein expression in the central nervous system, suprabasal layer of the epidermis, and hypertrophic cartilage. We have overexpressed this factor in CHO cells and have shown that, when these cells are introduced subcutaneously into nude, athymic mice, the secreted BMP-6 protein induces ectopic cartilage and bone in a pattern that recapitulates endochondral bone formation. We have also overexpressed BMP-6 within a pluripotent mesenchymal cell line and have shown that the protein acts as an autocrine factor that induces osteoblastic differentiation in vitro. (DBO)