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 investigate the effect on skeleton development of the combined absence of some Bmp genes expressed in the same areas, we have intercrossed heterozygous Bmp7 mice with Bmp2 +/-, Bmp4 +/-, or Bmp5 +/- animals. Bmp2/7 and Bmp5/7 double heterozygous animals do not present with any abnormalities. In contrast, Bmp4/7 double heterozygotes develop minor defects in two restricted areas of the skeleton, the rib cage, and the distal part of the limbs. In the ribs, Bmp4 and Bmp7 seem to act in the same pathway to assure proper guidance of mesenchymal condensations of the ribs extending toward the sternum. In the limbs, these molecules appear to play a similar role in controlling digit number, possibly through induction of apoptosis in the interdigital and anterior mesenchyme.
Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, USA.
T
T
Katagiri
S
S
Boorla
J L
JL
Frendo
B L
BL
Hogan
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G
Karsenty
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001842:Bone and Bones / Q000002:abnormalities*; D006579:Heterozygote; D017880:Limb Deformities, Congenital / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D012272:Ribs / Q000002:abnormalities*; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C525815:Bmp5 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta