SKELETAL ABNORMALITIES IN DOUBLY HETEROZYGOUS BMP4 AND BMP7 MICE

Analysis of the skeletal phenotypes caused by the genetic inactivation of individual Bmps, along with the study of their expression patterns , suggest possible functional redundancy of these molecules. To invest igate the effect on skeleton development of the combined absence of so me Bmp genes expressed in the same areas, we have intercrossed heteroz ygous Bmp7 mice with Bmp2(+/-), Bmp4(+/-), or Bmp5(+/-) animals. Bmp2/ 7 and Bmp5/7 double heterozygous animals do not present with any abnor malities. In contrast, Bmp4/7double heterozygotes develop minor defect s in hive restricted areas of the skeleton, the rib cage, and the dist al part of the limbs. In the ribs, Bmp4 and Bmp7 seem to act in the sa me pathway to assure proper guidance of mesenchymal condensations of t he ribs extending toward the sternum. In the limbs, these molecules ap pear to play a similar role in controlling digit number possibly throu gh induction of apoptosis in the interdigital and anterior mesenchyme. (C) 1998 Wiley-Liss, Inc.