Development of a transgenic mouse with R124H human TGFBI mutation associated with Avellino corneal dystrophy

Abstract

Purpose: To investigate the phenotype and predisposing factors of an Avellino corneal dystrophy transgenic mouse model.

Methods: Human TGFBI cDNA with R124H mutation was used to make a transgenic mouse expressing human protein (TGFBI^R124H mouse). Reverse transcription PCR (RT-PCR) was performed to analyze TGFBI^R124H expression. A total of 187 mice including 17 homozygotes, 85 heterozygotes and 85 wild-type mice were examined for phenotype. Affected mice were also examined by histology, immunohistochemistry and electron microcopy.

Results: RT-PCR confirmed the expression of TGFBI^R124H in homozygous mice. Corneal opacity defined as granular and lattice deposits was observed in 52.9% of homozygotes, 20.0% of heterozygotes. The incidence of corneal opacity was significantly higher in homozygotes than in heterozygotes. Histology of affected mice was similar to histology of human Avellino dystrophy. Lesions were Congo red and Masson Trichrome positive, and were observed as a deposit of amorphous material by electron microscopy. The incidence of corneal opacity was higher in aged mice in each group.

Conclusions: We established an Avellino dystrophy mouse model caused by R124H mutation of human TGFBI.