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.
Fleischmann
A
A
Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
Hafezi
F
F
Elliott
C
C
Remé
C E
CE
Rüther
U
U
Wagner
E F
EF
D000818:Animals; D021461:Animals, Outbred Strains; D017209:Apoptosis / Q000235:genetics; D001846:Bone Development / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D019281:Dimerization; D005314:Embryonic and Fetal Development / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D016762:Genes, fos; D005816:Genetic Complementation Test; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000473:pathology; D010022:Osteopetrosis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000196:embryology; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000502:physiology; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1