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PMID: 11069886 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 14 ·No. 21 ·2000-11-01 ·Pages 2695-700

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

Abstract

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.

MeSH Terms
Animals Animals, Outbred Strains Apoptosis/genetics Bone Development/genetics Cell Differentiation/drug effects Dimerization Embryonic and Fetal Development/genetics Fibroblasts/metabolism Gene Deletion Gene Expression Regulation Genes, fos Genetic Complementation Test Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Mice, Transgenic Osteoclasts/pathology Osteopetrosis/genetics Proto-Oncogene Proteins c-fos/deficiency,physiology Retinal Rod Photoreceptor Cells/embryology Structure-Activity Relationship Transcription Factor AP-1/chemistry,physiology
Chemicals
Proto-Oncogene Proteins c-fos Transcription Factor AP-1 fos-related antigen 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fleischmann A
Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
Hafezi F
Elliott C
Remé C E
Rüther U
Wagner E F
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.187900
Published
2000-11-01
Pages
2695-700
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317035
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.187900 PMC Full Text View journal details
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