A major limitation in FA research is the absence of an animal model that faithfully recapitulates the clinical features of this disease in humans. While mice have the characteristic DNA repair defects, they do not spontaneously develop the progressive anemia or acute leukemia seen in many patients. It is thought that the short lifespan of mice provides insufficient time for the development of the progressive bone marrow failure observed in patients. This proposal is potentially very significant as it will create the first large animal model of FA. Based on the remarkable success of the pig model of cystic fibrosis, it is anticipated that our proposed FANCA deficient pig will serve as an excellent model for studying FA disease progression and even more importantly, as a pre-clinical platform to test novel therapies. The research here will develop an animal model of cancers that occur due to mutations in FA genes, including five different breast cancer genes. The animal model can then be used to test the ability of differernt drugs to prevent tumor formation.
Researchers: William Fleming, Markus Grompe