Evidence mapPaperPMID 40465262Full record

ArticleInvestigative ophthalmology & visual science2025

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

Yuki Oyama, Suguru Ito, Taichi Yuasa, Mizuki Ueda, Satoshi Chiba, Tatsuya Nakagawa, Ayaka Izumi, Masahito Ikawa, Noriko Koizumi, Naoki Okumura

Abstract read
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Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Yuki OyamaDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Suguru ItoDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Taichi YuasaDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Mizuki UedaDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Satoshi ChibaDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Tatsuya NakagawaDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Ayaka IzumiActualEyes Inc., Kyotanabe, Japan.
Masahito IkawaGraduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Noriko KoizumiDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Naoki OkumuraDepartment of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 60 weeks, Tcf4+/(CTG)100 mice showed increased guttae percentage (0.314% ± 0.145%) versus wild-type (0.170% ± 0.089%), although not statistically significant. Tcf4(CTG)100/(CTG)100 mice exhibited significantly higher guttae formation (0.563% ± 0.293%) compared to controls. Similarly, endothelial cell density showed non-significant reduction in Tcf4+/(CTG)100 (1629 ± 71 cells/mm2) versus wild-type (1704 ± 68 cells/mm2), whereas Tcf4(CTG)100/(CTG)100 mice demonstrated significant decrease (1600 ± 76 cells/mm2). RNA sequencing identified 3221 differentially expressed genes (579 upregulated, 2,642 downregulated), with enrichment in pathways related to adaptive immune response, chemokine signaling, and cytokine-cytokine receptor interaction. Conclusions: Our study demonstrates that TNR expansion in the Tcf4 intron, on its own, is sufficient to induce FECD phenotypes in vivo. This mouse model provides a valuable tool for investigating FECD pathogenesis and developing targeted therapeutics.

Indexed as

Disease Models, AnimalFuchs' Endothelial DystrophyTranscription Factor 4Trinucleotide Repeat ExpansionAnimalsEndothelium, CornealGene Knock-In TechniquesMiceMice, Inbred C57BLPhenotypeTcf4 protein, mouseTranscription Factor 4

Identifiers

PMID40465262
PMCPMC12151262

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.