BMP7 NULL MUTATION IN MICE - DEVELOPMENTAL DEFECTS IN SKELETON, KIDNEY, AND EYE

While generating bcl2 alpha transgenic mice, we found some F2 offsprin g of one of the transgenic lines which were very small and had closed eyes at the time of weaning. These pups died within 1 month after birt h. In order to determine the molecular basis of this phenotype, we scr eened a genomic library of the above transgenic line with a transgene- specific probe and found that the Bmp7 gene, a member of the TGF beta superfamily, was inactivated by insertional mutagenesis due to transge ne integration. The Bmp7 homozygous null condition in mice is a postna tal lethal mutation and is associated with various developmental defec ts: holes in the basisphenoid bone and the xyphoid cartilage, retarded ossification of bones, fused ribs and vertebrae, underdeveloped neura l arches of the lumbar and sacral vertebrae, polydactyly of the hind l imbs, a kinked tail, a reduced number of nephrons, polycystic kidney, lack of retinal pigmentation, and retarded lens development. These fin dings indicate that BMP7 is an important signaling molecule for normal development of the mammalian skeleton, kidney, and eye. (C) 1997 Acad emic Press