Establishment of a transgenic mouse model of corneal dystrophy overexpressing human BIGH3

Liao, Xin; Cui, Hongping; Wang, Fang

doi:10.3892/ijmm.2013.1480

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…Thus, the study concludes that TGFBIp might be involved in anterior segment morphogenesis and eye development (Kim et al, 2007). Another mouse model overexpressing human TGFBIp under the control of the phosphoglycerate kinase promoter showed similar corneal opacities when eyelids opened at approximately two weeks after birth (Liao et al, 2013). This study did not perform any histological examination of the anterior segment of the transgenic mice, and we cannot conclude if the opacities are caused by TGFBIp accumulation or disrupted corneal endothelium.…”

Section: Overexpression Mouse Modelsmentioning

confidence: 82%

“…Protein domain 1 Phenotype 2 Age of onset (decade) Reference V113I FAS1-1 GCD1 Third (Zenteno et al, 2006) V113I/L558P FAS1-1/FAS1-4 Variant LCD Fourth -Fifth (Ann et al, 2017) D123H FAS1-1 Atypical GCD Fifth (Ha et al, 2003) R124C FAS1-1 LCD1 First -Second (Munier et al, 1997) R124C/G470Ter FAS1-1/FAS1-3 LCD1 Eighth (Sakimoto et al, 2003) R124C/A546D FAS1-1/FAS1-4 Variant LCD Second -Third (Cao et al, 2017) R124H FAS1-1 GCD2 First -Fourth (Munier et al, 1997) R124H/P130Ter FAS1-1 GCD2 Third (Yam et al, 2012) R124H/R179Ter FAS1-1 GCD2 Fourth (Song et al, 2015) R124H/N544S FAS1-1/FAS1-4 GCD2-LCD Seventh (Yamada et al, 2009) R124L FAS1-1 RBCD First -Second (Okada et al, 1998) R124L/T125- (Han et al, 2014) Overexpression (liver) Anterior segment dysgenesis (Kim et al, 2007) Overexpression Corneal opacities (Liao et al, 2013) R555W mutant (overexpressed) Retinal degeneration (Bustamante et al, 2008) R124H mutant Corneal opacities (Yamazoe et al, 2015)…”

Section: Mutationsmentioning

confidence: 99%

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Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

Nielsen

Poulsen

Lukassen

et al. 2020

Progress in Retinal and Eye Research

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Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-β-induced gene (TGFBI) are associated with amyloid and amorphous protein deposition in TGFBI-linked corneal dystrophies. We discuss the current understanding of the biochemical mechanisms of TGFBI-linked corneal dystrophies and propose that mutations leading to granular corneal dystrophy (GCD) decrease the solubility of TGFBIp and affect the interactions between TGFBIp and components of the corneal stroma, whereas mutations associated with lattice corneal dystrophy (LCD) lead to a destabilization of the protein that disrupts proteolytic turnover, especially by the serine protease HtrA1. Future research should focus on TGFBIp function in the cornea, confirmation of the biochemical mechanisms in vivo, and the development of disease models. Future therapies for TGFBI-linked corneal dystrophies might include topical agents that regulate protein aggregation or gene therapy that targets the mutant allele by CRISPR/Cas9 technology.

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Section: Overexpression Mouse Modelsmentioning

confidence: 82%

Section: Mutationsmentioning

confidence: 99%

Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

Nielsen

Poulsen

Lukassen

et al. 2020

Progress in Retinal and Eye Research

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“…However, mutated TGFBI was expressed in the retina and induced an age‐dependent retinal degeneration both functionally (ERG) and histologically, suggesting that altered TGFBI may affect photoreceptor survival. Using an identical promoter but a different transgenesis protocol, Liao, Cui, and Wang () established a transgenic mouse model overexpressing TGFBI. These mice displayed central corneal opacities in five out of seven transgenic mice…”

Section: Tgfbi Expression Role and Pathology In The Eye Of Humans Amentioning

confidence: 99%

“…photoreceptor survival. Using an identical promoter but a different transgenesis protocol,Liao, Cui, and Wang (2013) established a transgenic mouse model overexpressing TGFBI. These mice displayed central corneal opacities in five out of seven transgenic miceYamazoe et al (2015) reported a transgenic mouse model of GCD2 caused by the p.Arg124His variant, showing granular with or without lattice deposits in the center of the cornea.…”

mentioning

confidence: 99%

Mutation update:TGFBIpathogenic and likely pathogenic variants in corneal dystrophies

et al. 2019

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Human transforming growth factor β‐induced (TGFBI), is a gene responsible for various corneal dystrophies. TGFBI produces a protein called TGFBI, which is involved in cell adhesion and serves as a recognition sequence for integrins. An alteration in cell surface interactions could be the underlying cause for the progressive accumulation of extracellular deposits in different layers of the cornea with the resulting changes of refractive index and transparency. To this date, 69 different pathogenic or likely pathogenic variants in TGFBI have been identified in a heterozygous or homozygous state in various corneal dystrophies, including a novel variant reported here. All disease‐associated variants were inherited as autosomal‐dominant traits but one; this latter was inherited as an autosomal recessive trait. Most corneal dystrophy‐associated variants are located at amino acids Arg124 and Arg555. To keep the list of corneal dystrophy‐associated variant current, we generated a locus‐specific database for TGFBI (http://databases.lovd.nl/shared/variants/TGFBI) containing all pathogenic and likely pathogenic variants reported so far. Non‐disease‐associated variants are described in specific databases, like gnomAD and ExAC but are not listed here. This article presents the most recent up‐to‐date list of disease‐associated variants.

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“…58 Overexpression of an Arg155Trp TGFbI variant transgenic mouse resulted in retinal photoreceptor atrophy, 59 but the same insertional promotor and another transgenesis protocol resulted in mice with central corneal opacities that were not microscopically phenotyped. 60 Deletion of TGFbI did not result in any ocular lesions, and the reported increased incidence of spontaneous tumors and 7,12-dimethylbenz[a]anthracene-induced skin tumors in these TGFbI À/À mice 67 is small.…”

Section: Comparative Literature Review Of Corneal Dystrophy In Animalmentioning

confidence: 81%

Corneal Dystrophy in Dutch Belted Rabbits as a Possible Model of Thiel-Behnke Subtype of Epithelial-Stromal TGFβ-Induced Corneal Dystrophy

Schuh¹,

Holve

Mundwiler

2020

Toxicol Pathol

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The International Committee for Classification of Corneal Dystrophies (IC3D) categorized corneal dystrophies in humans using anatomic, genotypic, and clinicopathologic phenotypic features. Relative to the IC3D classification, a review of the veterinary literature confirmed that corneal dystrophy is imprecisely applied to any corneal opacity and to multiple poorly characterized histologic abnormalities of the cornea in animals. True corneal dystrophy occurs in mice with targeted mutations and spontaneously in pet dogs and cats and in Dutch belted (DB) rabbits, but these instances lack complete phenotyping or genotyping. Corneal dystrophy in DB rabbits can be an important confounding finding in ocular toxicology studies but has only been described once. Therefore, the ophthalmology and pathology of corneal dystrophy in 13 DB rabbits were characterized to determine whether the findings were consistent with or a possible model of any corneal dystrophy subtypes in humans. Slit lamp and optical coherence tomography (OCT) imaging were used to characterize corneal dystrophy over 4 months in young DB rabbits. The hyperechoic OCT changes correlated with light microscopic findings in the anterior stroma, consisting of highly disordered collagen fibers and enlarged keratocytes. Histochemical stains did not reveal abnormal deposits. Small clusters of 8 to 16 nm diameter curly fibers identified by transmission electron microscopy were consistent with Thiel-Behnke (TBCD) subtype of epithelial-stromal transforming growth factor β-induced dystrophies. Sporadic corneal dystrophy in DB rabbits appears to be a potential animal model of TBCD, but genotypic characterization will be required to confirm this categorization.

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Establishment of a transgenic mouse model of corneal dystrophy overexpressing human BIGH3

Cited by 7 publications

References 16 publications

Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies

Mutation update:TGFBIpathogenic and likely pathogenic variants in corneal dystrophies

Corneal Dystrophy in Dutch Belted Rabbits as a Possible Model of Thiel-Behnke Subtype of Epithelial-Stromal TGFβ-Induced Corneal Dystrophy

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