Generation of a Mouse Model of Fuchs Endothelial Corneal Dystrophy by Knock-in of CTG Trinucleotide Repeat Expansion in the TCF4 Gene.

ABSTRACT:

Purpose

Fuchs endothelial corneal dystrophy (FECD) is frequently associated with trinucleotide repeat (TNR) expansion in the TCF4 gene intron. The aim of this study was to establish a novel FECD mouse model with TNR expansion.

Methods

We used CRISPR/Cas9-mediated genome editing to generate knock-in mice carrying 100 CTG repeats in the Tcf4 intron. Corneal endothelial phenotypes were evaluated using specular microscopy and transmission electron microscopy. Transcriptome analysis was performed using RNA sequencing of corneal endothelial tissue from Tcf4(CTG)100/(CTG)100 and wild-type mice.

Results

Tcf4+/(CTG)100 and Tcf4(CTG)100/(CTG)100 mice developed characteristic FECD features, including progressive guttae formation and decreased corneal endothelial cell density. At

SUBMITTER: Oyama Y 

PROVIDER: S-EPMC12151262 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature