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J. Derek Thornton, Doug J. Swanson, Michelle N. Mary, Deqing Pei, Amy C. Martin, Stanley Pounds, Dan Goldowitz, Stephen X. Skapek; Persistent Hyperplastic Primary Vitreous Due to Somatic Mosaic Deletion of the Arf Tumor Suppressor. Invest. Ophthalmol. Vis. Sci. 2007;48(2):491-499. doi: https://doi.org/10.1167/iovs.06-0765.
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purpose. Mice lacking the Arf tumor-suppressor gene develop eye disease reminiscent of persistent hyperplastic primary vitreous (PHPV). The current work explores mechanisms by which Arf promotes eye development, and its absence causes a PHPV-like disease.
methods. Chimeric mice were made by fusing wild-type and Arf −/− morulae. In these experiments, wild-type cells are identified by transgenic expression of GFP from a constitutive promoter. PCR-based genotyping and quantitative analyses after immunofluorescence staining of tissue and cultured cells documented the relative contribution of wild-type and Arf −/− cells to different tissues in the eye and different types of cells in the vitreous.
results. The contributions of the Arf −/− lineage to the tail DNA, cornea, retina, and retina pigment epithelium (RPE) correlated with each other in wild-type↔Arf −/− chimeric mice. Newborn chimeras had primary vitreous hyperplasia, evident as a retrolental mass. The mass was usually present when the proportion of Arf −/− cells was relatively high and absent when the Arf −/− proportion was low. The Pdgfrβ- and Sma-expressing cells within the mass arose predominantly from the Arf −/− population. Ectopic Arf expression induced smooth muscle proteins in cultured pericyte-like cells, and Arf and Sma expression overlapped in hyaloid vessels.
conclusions. In the mouse model, loss of Arf in only a subset of cells causes a PHPV-like disease. The data indicate that both cell autonomous and non–cell autonomous effects of Arf may contribute to its role in vitreous development.
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