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I. Ajioka, B.A. Schweers, M.A. Dyer; Investigation Of The Individual Role Of Rb Family Proteins In The Mouse Retinal Development . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2783.
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The timing of cell cycle exit is coordinated with cell–fate specification and differentiation in the developing central nervous system to ensure that the appropriate number of neurons and glia are generated in the correct proportion. If too many neural progenitor cells exit the cell cycle during the early stages of development, then the overall number of cells is reduced and the ratio of cell types shifts. Genetically engineered mice carrying targeted deletion of genes that regulate cell cycle progression have been used to study the coordination of proliferation and cell–fate specification during development.The protein product of the retinoblastoma susceptibility gene (Rb), pRB, and the related p107 and p130 proteins regulate transitions between cell proliferation and terminal differentiation. Although they all bind to E2F family that regulates the expression of numerous genes needed for cell cycle progression, some E2F family proteins specifically bind to the specific Rb family protein, suggesting that each Rb family protein has both specific and unique functions. Using Cre–expressing retroviruses and a retinal progenitor–specific Cre transgenic mouse line mated to Rblox mice, we previously showed that a cell–autonomous requirement for Rb at specific developmental stages in retinal progenitor cells and rod photoreceptors (Zhang, J. et al. (2004) Nat. Genet. 36, 351–360). On the other hand, we found the compensational effects of pRb and p107 on retinal progenitor cells (Schweers, B.A. et al. (submitted)).
To elucidate the individual role of the Rb family proteins during retinal development, we are generating and analyzing one–allele pRb, p107 or p130 mice on pRb conditional and both p107 and p130 knockout mouse line.
These mice show the abnormal retinal development.
These studies confirm that each Rb family member plays unique and overlapping roles in retinal development.
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