Overexpression of fra-2 in transgenic mice perturbs normal eye development.
The major components of transcription factor AP-1 (Activator Protein 1) are encoded by the two families of genes related to the proto-oncogenes c-fos and c-jun. The fos-related antigen-2 (fra-2) gene is the most recently described member of the Fos family. To determine the oncogenic potential of fra-2, transgenic mice were generated which over-express fra-2 in a number of tissues. No tumours were evident in any transgenic mice up to 18 months of age, although eye development was severely disrupted in these animals. Corneal abnormalities could be observed histologically as early as embryonic day 15.5 and eyelid fusion failed to occur. Adult eyes were characterized by generalized anterior segment dysgenesis similar to that previously reported in transgenic mice over-expressing transforming growth factor alpha (TGF alpha), and occasionally microphthalmia. Expression of fra-2 was shown to increase following TGF alpha treatment of cells in vitro, suggesting that AP-1 complexes containing Fra-2 contribute to TGF alpha signalling events.
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Camberra ACT.
J Z
JZ
McHenry
A
A
Leon
K I
KI
Matthaei
D R
DR
Cohen
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001824:Body Constitution / Q000235:genetics; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics*; D005123:Eye / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D005124:Eye Abnormalities / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D051921:Fos-Related Antigen-2; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D006651:Histocytochemistry; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D019076:Transgenes / Q000187:drug effects / Q000235:genetics*
D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha