| Title: |
Systematic Ocular Phenotyping of Knockout Mouse Lines Identifies Genes Associated With Age-Related Corneal Dystrophies |
| Authors: |
Briere, Andrew; Vo, Peter; Yang, Benjamin; Adams, David; Amano, Takanori; Amarie, Oana; Berberovic, Zorana; Bower, Lynette; Brown, Steve; Burrill, Samantha; Cho, Soo Young; Clementson-Mobbs, Sharon; d'Souza, Abigail; Eskandarian, Mohammad; Flenniken, Ann; Fuchs, Helmut; Gailus-Durner, Valerie; Hérault, Yann; Hrabe de Angelis, Martin; Jin, Shundan; Joynson, Russell; Kang, Yeon Kyung; Kim, Haerim; Masuya, Hiroshi; Meziane, Hamid; Nam, Ki-Hoan; Noh, Hyuna; Nutter, Lauryl; Palkova, Marcela; Prochazka, Jan; Raishbrook, Miles Joseph; Riet, Fabrice; Salazar, Jason; Sedlacek, Radislav; Selloum, Mohammed; Seo, Kyoung Yul; Seong, Je Kyung; Shin, Hae-Sol; Shiroishi, Toshihiko; Stewart, Michelle; Svenson, Karen; Tamura, Masaru; Tolentino, Heather; Wells, Sara; Wurst, Wolfgang; Yoshiki, Atsushi; Lanoue, Louise; Lloyd, K. C. Kent; Leonard, Brian; Roux, Michel; Mckerlie, Colin; Moshiri, Ala |
| Contributors: |
Touro University; California Northstate University (CNSU); University of California (UC); The Wellcome Trust Sanger Institute Cambridge; RIKEN BioResource Research Center Tsukuba, Japan (RIKEN BRC); Helmholtz Zentrum München = German Research Center for Environmental Health (HMGU); Lunenfeld-Tanenbaum Research Institute Toronto, Canada; University of California Davis (UC Davis); MRC Harwell Institute UK; The Jackson Laboratory Bar Harbor (JAX); Hanyang University; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Technische Universität Munchen = Technical University Munich = Université Technique de Munich (TUM); German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung Neuherberg (DZD); Seoul National University Seoul (SNU); Korea Research Institute of Bioscience & Biotechnology (KRIBB); The Hospital for sick children Toronto (SickKids); Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS); Czech Academy of Sciences Prague (CAS); Yonsei University; University of Toronto |
| Source: |
ISSN: 0146-0404. |
| Publisher Information: |
CCSD; Association for Research in Vision and Ophthalmology |
| Publication Year: |
2025 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| Description: |
International audience ; Purpose: This study investigates genes contributing to late-adult corneal dystrophies (LACDs) in aged mice, with potential implications for late-onset corneal dystrophies (CDs) in humans.Methods: The International Mouse Phenotyping Consortium (IMPC) database, containing data from 8901 knockout mouse lines, was filtered to include late-adult mice (49+ weeks) with significant (P < 0.0001) CD phenotypes. Candidate genes were mapped to human orthologs using the Mouse Genome Informatics group, with expression analyzed via PLAE and a literature review for prior CD associations. Comparative analyses of LACD genes from IMPC and established human CD genes from IC3D included protein interactions (STRING), biological processes (PANTHER), and molecular pathways (KEGG).Results: Analysis identified 14 genes linked to late-adult abnormal corneal phenotypes. Of these, 2 genes were previously associated with CDs in humans, while 12 were novel. Seven of the 14 genes (50%) were expressed in the human cornea based on single-cell transcriptomics. Protein-protein interactions via STRING showed several significant interactions with known human CD genes. PANTHER analysis identified six biological processes shared with established human CD genes. Two genes (Rgs2 and Galnt9) were involved in pathways related to human corneal diseases, including cGMP-PKG signaling, mucin-type O-glycan biosynthesis, and oxytocin signaling. Other candidates were implicated in pathways such as pluripotency of stem cells, MAPK signaling, WNT signaling, actin cytoskeleton regulation, and cellular senescence.Conclusions: This study identified 14 genes linked to LACD in knockout mice, 12 of which are novel in corneal biology. These genes may serve as potential therapeutic targets for treating corneal diseases in aging human populations. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1167/iovs.66.5.7 |
| Availability: |
https://hal.science/hal-05227476; https://hal.science/hal-05227476v1/document; https://hal.science/hal-05227476v1/file/Briere%20et%20al.%20-%202025%20-%20Systematic%20Ocular%20Phenotyping%20of%20Knockout%20Mouse%20Lines%20Identifies%20Genes%20Associated%20With%20Age-Related%20C.pdf; https://doi.org/10.1167/iovs.66.5.7 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.C3B4D10E |
| Database: |
BASE |