Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development

Cell. 1997 May 30;89(5):765-71. doi: 10.1016/s0092-8674(00)80259-7.

Abstract

We have generated Cbfa1-deficient mice. Homozygous mutants die of respiratory failure shortly after birth. Analysis of their skeletons revealed an absence of osteoblasts and bone. Heterozygous mice showed specific skeletal abnormalities that are characteristic of the human heritable skeletal disorder, cleidocranial dysplasia (CCD). These defects are also observed in a mouse Ccd mutant for this disease. The Cbfa1 gene was shown to be deleted in the Ccd mutation. Analysis of embryonic Cbfa1 expression using a lacZ reporter gene revealed strong expression at sites of bone formation prior to the earliest stages of ossification. Thus, the Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the Cbfa1 heterozygous mouse is a paradigm for a human skeletal disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Development / genetics*
  • Cell Differentiation / genetics
  • Cleidocranial Dysplasia / genetics*
  • Core Binding Factor Alpha 1 Subunit
  • Gene Deletion
  • Gene Targeting
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Neoplasm Proteins*
  • Osteoblasts / pathology*
  • Syndrome
  • Transcription Factors / genetics*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Neoplasm Proteins
  • Transcription Factors