title: Ocular abnormalities in mice lacking the Ski proto-oncogene.
abstract: OBJECTIVE
  Persistent hyperplastic primary vitreous (PHPV) is a developmental ocular malformation often associated with additional ocular abnormalities. This study involved a novel mouse model of PHPV, generated by a null mutation of the Ski proto-oncogene, that displays other anterior segment and retinal malformations often found in human cases of PHPV.
  
  
  METHODS
  Morphologic and histologic analyses of Ski-/- mice were used to document ocular abnormalities in comparison to those of normal littermates. Immunohistochemical studies were used to examine the expression of relevant markers of ocular and vascular development including Pax6, beta-III tubulin, and Flk1.
  
  
  RESULTS
  PHPV and microphthalmia were found in 100% of Ski-/- fetuses. Other abnormalities included anterior segment and lens dysgenesis, retinal folds, chorioretinal coloboma, and Peters anomaly. The severity was variable, even in a highly homogeneous genetic background. PHPV was characterized by the presence of retrolental fibrous and vascular tissue that did not express the neuronal marker beta-III tubulin, but was positive for Flk1 expression and contained no obviously pigmented cells.
  
  
  CONCLUSIONS
  The results show that normal ocular development requires the function of the Ski proto-oncogene, and mice lacking Ski have many features associated with PHPV, and some similarities with Peters anomaly in humans. Defects in Ski-/- mice closely resemble those described in animals lacking several of the retinoic acid receptor genes, or in animals exposed to excess retinoic acid during gestation. Ski has been shown to repress transcription induced by retinoic acid signaling, and may thus affect ocular development by regulating RA signaling.
authors.affiliation: Center for Genetic Eye Diseases, Cole Eye Institute, Cleveland, OH 44195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: McGannon
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Pankaj C
authors.initials: PC
authors.lastname: Gupta
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Clemencia
authors.initials: C
authors.lastname: Colmenares
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D005124:Eye Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008850:Microphthalmos / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014822:Vitreous Body / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C512653:Ski protein, mouse; D014404:Tubulin; D040301:Vascular Endothelial Growth Factor Receptor-2