title: Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the arf tumor suppressor.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105, USA.
authors.forename: J Derek
authors.initials: JD
authors.lastname: Thornton
authors.forename: Doug J
authors.initials: DJ
authors.lastname: Swanson
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Mary
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: Amy C
authors.initials: AC
authors.lastname: Martin
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.forename: Dan
authors.initials: D
authors.lastname: Goldowitz
authors.forename: Stephen X
authors.initials: SX
authors.lastname: Skapek
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004195:Disease Models, Animal; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000235:genetics; D006822:Hybrid Cells; D006965:Hyperplasia; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009030:Mosaicism; D014822:Vitreous Body / Q000002:abnormalities* / Q000098:blood supply* / Q000473:pathology
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins