To study the cooperativity of Fos and the tumor suppressor genes p53 and Rb in the pathogenesis of osteosarcoma in vivo transgenic mice overexpressing exogenous Fos will be crossed with mice deficient for p53 and mice with an inactivated I gene. The phenotype of the offspring will be characterized and compared to littermates expressing only the Fos transgen
Analysis of the murine transgene. and derived cell lines will include morphology and the expression of AP-1-associated genes as well as skeletal markers. The same investigations will be performed for tissues and cell lines derived from neoplastic and non-neoplastic human bone. The second objective of the research project is to generate transgenic mice overexpressing Fra-l to study the effect of this member of the Fos gene family on bone formation und tumorigenesis. By crossing Fra-l transgenic mice with Fos mutant mice, the issue of genetic rescue of the osteopetrotic phenotype of Fos mutant mice will be addressed. Training content (objective, benefit and expected impact)
The work at the l.M.P. will provide me with an intensive training in the molecular basis of bone diseases, especially of bor tumors. The laboratory training will include standard techniques, but also demanding in vivo methods. The training will enable me to perform independent biomedical research later.