title: Anterior segment dysgenesis after overexpression of transforming growth factor-beta-induced gene, beta igh3, in the mouse eye.
abstract: OBJECTIVE
  Beta igh3 is a transforming growth factor-beta-inducible cell adhesion molecule and its mutations are responsible for human autosomal dominant corneal dystrophies. Previously, we have studied the molecular properties of beta igh3 in vitro and reported that beta igh3 polymerizes to form a fibrillar structure and interacts with several extracellular matrix proteins including type I collagen. This study aimed to understand the role of elevated circulating levels of normal beta igh3 in eye development and corneal diseases.
  
  
  METHODS
  We generated Alb-hss igh3 transgenic mice that have liver-specific expression of human beta igh3 (hss igh3) under the control of the albumin (Alb) enhancer/promoter and investigated the influence of beta igh3 overexpression in mouse eye. Polymerase chain reaction (PCR) genotyping, western blotting, and ELISA were performed to generate Alb-hss igh3 transgenic mouse lines. To identify the ocular pathology, electron microscopy and histological staining were employed in Alb-hss igh3 transgenic mice and wild-type mice.
  
  
  RESULTS
  Normal hss igh3 was ectopically overexpressed in the liver, secreted into blood stream, and reached the cornea of Alb-hss igh3 transgenic mice. Among transgenic mice, some mice had anterior segment defects including corneal opacity, disorganization of the collagen layers in the corneal stroma, and corneolenticular adhesion.
  
  
  CONCLUSIONS
  These results suggest that beta igh3 may be involved in anterior segment morphogenesis and eye development in mice. In addition, this indicates that the level of normal beta igh3 expression must be properly maintained during ocular development. The phenotype observed in Alb-hss igh3 transgenic mice is similar to human eye disorders such as anterior segment dysgenesis and Peters' anomaly. Thus, this model provides a very useful tool to study human eye diseases and the control of proliferation and differentiation of neural crest-originated cells.
authors.affiliation: Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Min-Su
authors.initials: MS
authors.lastname: Han
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Bae
authors.forename: Hong-Kyun
authors.initials: HK
authors.lastname: Kim
authors.forename: Tae-Im
authors.initials: TI
authors.lastname: Kim
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000002:abnormalities* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D003316:Corneal Diseases / Q000209:etiology; D003318:Corneal Opacity / Q000209:etiology; D003319:Corneal Stroma / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000378:metabolism*; D005123:Eye / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007905:Lens Diseases / Q000209:etiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010641:Phenotype; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*; D000099222:betaIG-H3 Protein
chemical_list: D003094:Collagen; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein