title: KLEIP deficiency in mice causes progressive corneal neovascular dystrophy.
abstract: OBJECTIVE
  The BTB-kelch protein KLEIP/KLHL20 is an actin binding protein that regulates cell-cell contact formation and cell migration. The aim of our study was to characterize KLEIP's function in ocular health and disease in mice.
  
  
  METHODS
  KLEIP(-/-) mice were generated, and corneas were examined histologically and stained for keratin-1, loricrin, keratin-12, keratin-14, CD31, LYVE-1, F4/80, E-cadherin, and Ki67. Corneal abrasions were performed after eyelid opening.
  
  
  RESULTS
  Corneas of KLEIP(+/+) and KLEIP(-/-) mice were indistinguishable at birth. After eyelid opening corneal epithelial hyperplasia started to manifest in KLEIP(-/-) mice, showing a progressive epithelial metaplasia leading to total corneal opacity. In KLEIP(-/-) mice the initial stratified squamous corneal epithelium was altered to an epidermal histo-architecture showing several superficial keratinized cells, cell infiltrations into the stroma, and several apoptotic cells. Skin markers keratin 1 and loricrin were positive, and surface disease was accompanied by deep stromal vascularization. Expression analysis for E-cadherin in KLEIP(-/-) corneas showed acellular areas in the squamous epithelium, indicating a progressive fragile corneal integrity. Removal of the virgin epithelium accelerated strongly development of the epithelial and stromal alterations, identifying mechanical injuries as the major trigger for corneal dystrophy formation and scarification in KLEIP(-/-) mice.
  
  
  CONCLUSIONS
  The data identify KLEIP as an important molecule regulating corneal epithelial integrity.
authors.affiliation: Dept. of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University Germany, Ludolf-Krehl-Strasse 13-17, Mannheim, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Hahn
authors.forename: Christian T
authors.initials: CT
authors.lastname: Dietz
authors.forename: Sandra
authors.initials: S
authors.lastname: Kühl
authors.forename: Urs
authors.initials: U
authors.lastname: Vossmerbaeumer
authors.forename: Jens
authors.initials: J
authors.lastname: Kroll
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D016510:Corneal Neovascularization / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003318:Corneal Opacity / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C550011:KLHL20 protein, human; D012333:RNA, Messenger