Anterior segment dysgenesis after overexpression of transforming growth factor-β-induced gene, βigh3, in the mouse eye

Jung Eun Kim, Min Su Han, Yong Chul Bae, Hong Kyun Kim, Tae Im Kim, Eung Kweon Kim, In San Kim

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Abstract

Purpose: βigh3 is a transforming growth factor-β-inducible cell adhesion molecule and its mutations are responsible for human autosomal dominant corneal dystrophies. Previously, we have studied the molecular properties of βigh3 in vitro and reported that βigh3 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 βigh3 in eye development and corneal diseases. Methods: We generated Alb-hβigh3 transgenic mice that have liver-specific expression of human βigh3 (hβigh3) under the control of the albumin (Alb) enhancer/promoter and investigated the influence of βigh3 overexpression in mouse eye. Polymerase chain reaction (PCR) genotyping, western blotting, and ELISA were performed to generate Alb-hβigh3 transgenic mouse lines. To identify the ocular pathology, electron microscopy and histological staining were employed in Alb-hβigh3 transgenic mice and wild-type mice. Results: Normal hβigh3 was ectopically overexpressed in the liver, secreted into blood stream, and reached the cornea of Alb-hβigh3 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 βigh3 may be involved in anterior segment morphogenesis and eye development in mice. In addition, this indicates that the level of normal βigh3 expression must be properly maintained during ocular development. The phenotype observed in Alb-hβigh3 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.

Original languageEnglish
Pages (from-to)1942-1952
Number of pages11
JournalMolecular vision
Volume13
Publication statusPublished - 2007 Oct 16

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All Science Journal Classification (ASJC) codes

  • Ophthalmology

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