Evidence map›Paper›PMID 39833678›Full record

ArticleBMC genomics2025

Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes.

Peter Vo, Denise M Imai-Leonard, Benjamin Yang, Andrew Briere, Andy Shao, M Isabel Casanova, David Adams, Takanori Amano, Oana Amarie, Zorana Berberovic and 58 more

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In one paragraph

Article in BMC genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

68 authors.

Peter VoCalifornia Northstate University College of Medicine, Elk Grove, CA, USA.
Denise M Imai-LeonardDepartment of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis, Sacramento, CA, USA.
Benjamin YangUniversity of California Davis School of Medicine, Sacramento, CA, USA.
Andrew BriereTouro University California College of Medicine, Vallejo, CA, USA.
Andy ShaoDepartment of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Sacramento, CA, USA.
M Isabel CasanovaDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
David AdamsThe Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Takanori AmanoRIKEN BioResource Research Center, Tsukuba, Japan.
Oana AmarieInstitute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany.
Zorana BerberovicThe Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Lynette BowerMouse Biology Program, University of California Davis, Davis, CA, USA.
Robert BraunThe Jackson Laboratory, Bar Harbor, ME, USA.
Steve BrownMedical Research Council, Harwell Institute, Harwell, UK.
Samantha BurrillThe Jackson Laboratory, Bar Harbor, ME, USA.
Soo Young ChoDepartment of Molecular and Life Science, Hanyang University, Seoul, Republic of Korea.
Sharon Clementson-MobbsMary Lyon Centre, Medical Research Council, Harwell Institute, Harwell, UK.
Abigail D'SouzaThe Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Mary DickinsonDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Mohammad EskandarianThe Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Ann M FlennikenThe Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Helmut FuchsInstitute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany.
Valerie Gailus-DurnerInstitute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany.
Jason HeaneyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Yann HéraultUniversité de Strasbourg, CNRS UMR 7104, INSERM U 1258, IGBMC, Institut Clinique de la Souris, PHENOMIN, Illkirch-Graffenstaden, France.
Martin Hrabe de AngelisInstitute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany.
Chih-Wei HsuDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Shundan JinRIKEN BioResource Research Center, Tsukuba, Japan.
Russell JoynsonMary Lyon Centre, Medical Research Council, Harwell Institute, Harwell, UK.
Yeon Kyung KangCollege of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Haerim KimLaboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Hiroshi MasuyaRIKEN BioResource Research Center, Tsukuba, Japan.
Hamid MezianeUniversité de Strasbourg, CNRS UMR 7104, INSERM U 1258, IGBMC, Institut Clinique de la Souris, PHENOMIN, Illkirch-Graffenstaden, France.
Steve MurrayThe Jackson Laboratory, Bar Harbor, ME, USA.
Ki-Hoan NamLaboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Hyuna NohCollege of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Lauryl M J NutterThe Centre for Phenogenomics, The Hospital for Sick Children, Toronto, ON, Canada.
Marcela PalkovaCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
Jan ProchazkaCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
Miles Joseph RaishbrookCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
Fabrice RietUniversité de Strasbourg, CNRS UMR 7104, INSERM U 1258, IGBMC, Institut Clinique de la Souris, PHENOMIN, Illkirch-Graffenstaden, France.
Jennifer RyanThe Jackson Laboratory, Bar Harbor, ME, USA.
Jason SalazarMouse Biology Program, University of California Davis, Davis, CA, USA.
Zachery SeaveyThe Jackson Laboratory, Bar Harbor, ME, USA.
John Richard SeavittDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Radislav SedlacekCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
Mohammed SelloumUniversité de Strasbourg, CNRS UMR 7104, INSERM U 1258, IGBMC, Institut Clinique de la Souris, PHENOMIN, Illkirch-Graffenstaden, France.
Kyoung Yul SeoDepartment of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Je Kyung SeongLaboratory of Developmental Biology and Genomics, Research Institute of Veterinary Science, BK21 Plus Program for Advanced Veterinary Science, College of Veterinary Medicine and Interdisciplinary Program for Bioinformatics, Seoul National University, Seoul, Republic of Korea.
Hae-Sol ShinDepartment of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Toshihiko ShiroishiRIKEN BioResource Research Center, Tsukuba, Japan.
Michelle StewartMary Lyon Centre, Medical Research Council, Harwell Institute, Harwell, UK.
Karen SvensonThe Jackson Laboratory, Bar Harbor, ME, USA.
Masaru TamuraRIKEN BioResource Research Center, Tsukuba, Japan.
Heather TolentinoMouse Biology Program, University of California Davis, Davis, CA, USA.
Uchechukwu UdensiDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Sara WellsMary Lyon Centre, Medical Research Council, Harwell Institute, Harwell, UK.
Jacqueline WhiteThe Jackson Laboratory, Bar Harbor, ME, USA.
Amelia WillettThe Jackson Laboratory, Bar Harbor, ME, USA.
Janine WottonThe Jackson Laboratory, Bar Harbor, ME, USA.
Wolfgang WurstInstitute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Atsushi YoshikiRIKEN BioResource Research Center, Tsukuba, Japan.
International Mouse Phenotyping Consortium
Louise LanoueMouse Biology Program, University of California Davis, Davis, CA, USA.
K C Kent LloydMouse Biology Program, University of California Davis, Davis, CA, USA.
Brian C LeonardDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Michel J RouxUniversité de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, Illkirch, F-67400, France.
Colin McKerlieThe Centre for Phenogenomics, The Hospital for Sick Children, Toronto, ON, Canada.
Ala MoshiriDepartment of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Sacramento, CA, USA. amoshiri@ucdavis.edu.

Funding

UM1HG006348: Cas9 Genome Integrity Supplemental ProposalUM1HG006348 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI Jason D. Heaney, Chih-Wei Logan Hsu · 2016 to 2026
$47.5M
The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)UM1OD023222 · OD · JACKSON LABORATORY · PI ROBERT E BRAUN, Stephen A Murray · 2016 to 2026
$47.2M
KOMP2-Phase3 Production and Phenotyping by the DTCC Consortium TCP Transfer to UC DavisUM1OD023221 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KC KENT LLOYD · 2016 to 2026
$45.7M
UCD Mutant Mouse Regional Resource CenterU42OD012210 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KC KENT LLOYD · 2012 to 2026
$29.2M
Mouse Phenotyping Informatics Infrastructure - MP12UM1HG006370 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Pilar Cacheiro Martinez, Helen Elizabeth Parkinson · 2016 to 2026
$20.4M
KOMP Phase II Mouse Production and CryopreservationU42OD011175 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2012 to 2015
$18.9M
KOMP Phase II Mouse PhenotypingU54HG006364 · NHGRI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2011 to 2015
$16.3M
Intravitreal gene therapy for inherited retinal diseaseR01EY034123 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALA MOSHIRI · 2023 to 2026
$2.7M
Interrogation and Interpretation of Common Fund Data Sets to Identify Novel Ocular Disease GenesR03OD032622 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MOSHIRI, ALA · 2021 to 2021
$315k
Genome Canada OGI-051Horizon 2020 Framework Programme 653961INFRAFRONTIER 01KX1012NEI NIH HHS R01 EY034123NHGRI NIH HHS U54 HG006364NHGRI NIH HHS UM1 HG006348NHGRI NIH HHS UM1 HG006370NIH HHS R03 OD032622NIH HHS R03OD032622NIH HHS U42 OD011175NIH HHS U42 OD012210NIH HHS U54HG006364NIH HHS UM1 OD023221NIH HHS UM1 OD023222
6 · The paper itself

Abstract

purposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans.

methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P < 0.0001) abnormal cornea morphology to identify candidate CD genes. Corneal abnormalities were investigated by histopathology. A literature search was used to determine the proportion of candidate genes previously associated with CDs in mice and humans. Phenotypes of human orthologues of mouse candidate genes were compared with known human CD genes to identify protein-protein interactions and molecular pathways using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes.

resultsAnalysis of data from 8,707 knockout mouse lines identified 213 candidate CD genes. Of these, 37 (17%) genes were previously known to be associated with CD, including 14 in the mouse, 16 in humans, and 7 in both. The remaining 176 (83%) genes have not been previously implicated in CD. We also searched publicly available RNAseq data and found that 131 of the total 213 (61.5%) were expressed in adult human corneal tissue. STRING analysis showed several interactions within and between candidate and established CD proteins. All cellular pathways of the established genes were found in the PANTHER analysis of the candidate genes. Several of the candidate genes were implicated in corneal disease, such as TGF-ß signaling. We also identified other possible underappreciated mechanisms relevant to the human cornea.

conclusionsWe identified 213 mouse genes that resulted in statistically significant abnormal corneal phenotypes in knockout mice, many of which have not previously been implicated in corneal pathology. Bioinformatic analyses implicated candidate genes in several signaling pathways which are potential therapeutic targets.

Indexed as

CorneaCorneal Dystrophies, HereditaryAnimalsHumansMiceMice, KnockoutPhenotypeCorneal diseaseCorneal dysmorphologiesCorneal dystrophies

Identifiers

PMID39833678
PMCPMC11744888

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