Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the Arf tumor suppressor

J. Derek Thornton, Doug J. Swanson, Michelle N. Mary, Deqing Pei, Amy C. Martin, Stanley Pounds, Dan Goldowitz, Stephen X. Skapek

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)491-499
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number2
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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