| First Author | Thornton JD | Year | 2007 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 48 |
| Issue | 2 | Pages | 491-9 |
| PubMed ID | 17251441 | Mgi Jnum | J:123332 |
| Mgi Id | MGI:3717996 | Doi | 10.1167/iovs.06-0765 |
| Citation | Thornton JD, et al. (2007) Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the arf tumor suppressor. Invest Ophthalmol Vis Sci 48(2):491-9 |
| abstractText | 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 Pdgfrbeta- 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. |
