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Fra-1 replaces c-Fos-dependent functions in mice.

Structure-function analysis as well as studies with knock-out and transgenic mice have assigned distinct functions to c-Fos and Fra-1, two components of the transcription factor AP-1 (activator protein-1). To test whether Fra-1 could substitute for c-Fos, we generated knock-in mice that express Fra-1 in place of c-Fos. Fra-1 rescues c-Fos-dependent functions such as bone development and light-induced photoreceptor apoptosis. Importantly, rescue of bone cell differentiation, but not photoreceptor apoptosis, is gene-dosage dependent. Moreover, Fra-1 fails to substitute for c-Fos in inducing expression of target genes in fibroblasts. These results show that c-Fos and Fra-1 have maintained functional equivalence during vertebrate evolution.

Pubmed ID: 11069886


  • Fleischmann A
  • Hafezi F
  • Elliott C
  • Remé CE
  • Rüther U
  • Wagner EF


Genes & development

Publication Data

November 1, 2000

Associated Grants


Mesh Terms

  • Animals
  • Animals, Outbred Strains
  • Apoptosis
  • Bone Development
  • Cell Differentiation
  • Dimerization
  • Embryonic and Fetal Development
  • Fibroblasts
  • Gene Deletion
  • Gene Expression Regulation
  • Genes, fos
  • Genetic Complementation Test
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Osteoclasts
  • Osteopetrosis
  • Proto-Oncogene Proteins c-fos
  • Retinal Rod Photoreceptor Cells
  • Structure-Activity Relationship
  • Transcription Factor AP-1