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 RIS Download
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