Neural Tube, Skeletal and Body Wall Defects in Mice Lacking Transcription Factor AP-2

Nature. 1996 May 16;381(6579):238-41. doi: 10.1038/381238a0.

Abstract

The retinoic acid-inducible transcription factor AP-2 is expressed in epithelial and neural crest cell lineages during murine development. AP-2 can regulate neural and epithelial gene transcription, and is associated with overexpression of c-erbB-2 in human breast-cancer cell lines. To ascertain the importance of AP-2 for normal development, we have derived mice containing a homozygous disruption of the AP-2 gene. These AP-2-null mice have multiple congenital defects and die at birth. In particular, the AP-2 knockout mice exhibit anencephaly, craniofacial defects and thoraco-abdominoschisis. Skeletal defects occur in the head and trunk region, where many bones are deformed or absent. Analysis of these mice earlier in embryogenesis indicates a failure of cranial neural-tube closure and defects in cranial ganglia development. We have shown that AP-2 is a fundamental regulator of mammalian craniofacial development.

Publication types

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

MeSH terms

  • Animals
  • Bone and Bones / abnormalities*
  • Bone and Bones / embryology
  • Cranial Nerves / abnormalities
  • Cranial Nerves / embryology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Female
  • Fetus / abnormalities*
  • Fetus / ultrastructure
  • Immunoenzyme Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscles / abnormalities
  • Muscles / embryology
  • Neural Crest / cytology
  • Neural Crest / embryology
  • Neural Tube Defects / embryology*
  • Neural Tube Defects / genetics
  • Skull / abnormalities
  • Skull / embryology
  • Transcription Factor AP-2
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • Transcription Factor AP-2
  • Transcription Factors