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L. Kong, P.A. Overbeek; Involvement of Rb Gene in Different Cell Cycle Regulations to the Related Cells in the Eye . Invest. Ophthalmol. Vis. Sci. 2003;44(13):408.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To study the role of Rb gene in regulating cell cycle control in different ocular tissues by Cre-loxp mediated inactivation of Rb gene in the eye. Methods: Four transgenic families were generated and the expression of Cre was driven by modified Pax6 promoter. The expression pattern of Cre was characterized by cross-mating Pax6-Cre transgenic mice with Rosa26 reporter mice (R26R). The conditional Rb null mice were generated by triple mating of Pax6-Cre, Rb Δ20 and Rbloxp/loxp mice. Results: The cre mediated DNA recombination was found in the lens placode, epithelial cells of conjunctiva, cornea and mature lens. In the retina, the DNA recombination was found in the ganglion cell layer and inner nuclear cell layer after E15.5. The mice with Rb null in the eye have the phenotype of small eye and cataract. BrdU analysis showed that the lens fiber cells, which are postmitotic cells, re-enter the cell cycle and start proliferating. However, the lens epithelial cells, cornea epithelial cells and conjunctival epithelial cells function normally. No retinoblastoma was found in the eye. Cell cycle gene in situ hybridization showed that in the lens fiber cells, the expression of cyclin A2, cyclin B1 and cyclin E was upregulated. Instead of forming the tumor the lens fiber cells underwent p53 dependant cell death and developed cataract and microphthalmia. Conclusion: Our results show that loss of function of Rb gene is essential for the lens fiber cells get out of differentiating program and re-enter the cell cycle but is not sufficient enough to develop tumor. Most importantly, loss of function of pRb did not interrupt the cell cycle control in the mitotic cells such as lens epithelial cells, cornea epithelial cells and also retinal cells. These results suggest that Rb gene plays different role in the cell cycle regulation in the different cells in the eye. The cells with proliferating activity may have the other mechanisms of cell cycle regulation besides pRb. Our mouse model provides a stable in vivo model to study the role of Rb gene in regulating cell cycle controls in the related cells in the eye. This line of cre mice should contribute to the study of gene regulation in the eye development.
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