title: Role of INK4a locus in normal eye development and cataract genesis.
abstract: The murine INK4a locus encodes the critical tumor suppressor proteins, p16(INK4a) and p19(ARF). Mice lacking both p16(INK4a) and p19(ARF) (INK4a-/-) in their FVB/NJ genetic backgrounds developed cataracts and microophthalmia. Histopathologically, INK4a-/- mice showed defects in the developmental regression of the hyaloid vascular system (HVS), retinal dysplasia, and cataracts with numerous vacuolations, closely resembling human persistent hyperplastic primary vitreous (PHPV). Ocular defects, such as retinal fold and abnormal migration of lens fiber cells, were observed as early as embryonic day (E) 15.5, thereby resulting in the abnormal differentiation of the lens. We also found that ectopic expression of p16(INK4a) resulted in the induction of gammaF-crystallin, suggesting an important role of INK4a locus during mouse eye development, and also providing insights into the potential genetic basis of human cataract genesis.
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Molecular Therapy Research Center, Sungkyunkwan University School of Medicine, 300 Chonchon-Dong, Changan-Gu, Suwon 440-746, Republic of Korea.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Lee
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Choi
authors.forename: Jaewhan
authors.initials: J
authors.lastname: Song
authors.forename: Changwon
authors.initials: C
authors.lastname: Kee
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000378:metabolism*; D005123:Eye / Q000098:blood supply / Q000196:embryology* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D040641:Quantitative Trait Loci / Q000235:genetics*; D015792:Retinal Dysplasia / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000172:deficiency / Q000378:metabolism*; D038222:gamma-Crystallins / Q000096:biosynthesis
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D038222:gamma-Crystallins