Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2.
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.
Zhang
J
J
Department of Biology, Yale University, New Haven, Connecticut 06511, USA.
Hagopian-Donaldson
S
S
Serbedzija
G
G
Elsemore
J
J
Plehn-Dujowich
D
D
McMahon
A P
AP
Flavell
R A
RA
Williams
T
T
D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology; D003391:Cranial Nerves / Q000002:abnormalities / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000002:abnormalities* / Q000648:ultrastructure; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000002:abnormalities / Q000196:embryology; D009432:Neural Crest / Q000166:cytology / Q000196:embryology; D009436:Neural Tube Defects / Q000196:embryology* / Q000235:genetics; D012886:Skull / Q000002:abnormalities / Q000196:embryology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors