Mice are Resistant to Retinoblastoma Due to Reciprocal Compensation Among Rb Family Members During Development

Abstract

Abstract: : In humans, retinoblastoma results from the inactivation of the RB gene in retinal progenitor cells during development. In mice, Rb deficient retinal progenitor cells do not form retinoblastoma. Purpose: We have carried out a series of genetic experiments to explore the mechanims that prevents retinoblastoma formation in mice. Methods: Using a variety of genetic approaches including Rb family knockout mice and conditional knockout mice, Cre transgenic mice and Cre retrovirues we tested the role of each Rb family member in regulating retinal progenitor cell proliferation during development. Results: The expression of the Rb family of genes (Rb, p107 and p130) is dynamic and largely non–overlapping during mouse retinal development. The pattern of expression in the human retina and the primate retina is distinct from that seen in mice. We have found that mouse retinal progenitor cells undergo reciprocal functional compensation among Rb family members when one gene is inactivated. Our preliminary data suggest that such functional compensation does not occur in human retinal progenitor cells. Conclusions: These data suggest that there is a complex feedback mechanism to prevent retinoblastoma in mice that involves reciprocal compensation among Rb family members during development.  

Keywords: gene/expression • retinal development • retinoblastoma