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, Eungkweon Kim, In San Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

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

Fingerprint

Transforming Growth Factors
Transgenic Mice
Albumins
Genes
Eye Diseases
Corneal Diseases
Anterior Eye Segment
Corneal Opacity
Corneal Stroma
Neural Crest
Extracellular Matrix Proteins
Liver
Cell Adhesion Molecules
Collagen Type I
Morphogenesis
Cornea
Electron Microscopy
Collagen
Western Blotting
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Kim, Jung Eun ; Han, Min Su ; Bae, Yong Chul ; Kim, Hong Kyun ; Kim, Tae-im ; Kim, Eungkweon ; Kim, In San. / Anterior segment dysgenesis after overexpression of transforming growth factor-β-induced gene, βigh3, in the mouse eye. In: Molecular Vision. 2007 ; Vol. 13. pp. 1942-1952.
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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.",
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Anterior segment dysgenesis after overexpression of transforming growth factor-β-induced gene, βigh3, in the mouse eye. / Kim, Jung Eun; Han, Min Su; Bae, Yong Chul; Kim, Hong Kyun; Kim, Tae-im; Kim, Eungkweon; Kim, In San.

In: Molecular Vision, Vol. 13, 16.10.2007, p. 1942-1952.

Research output: Contribution to journalArticle

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AU - Kim, Jung Eun

AU - Han, Min Su

AU - Bae, Yong Chul

AU - Kim, Hong Kyun

AU - Kim, Tae-im

AU - Kim, Eungkweon

AU - Kim, In San

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N2 - 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.

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