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Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes
Corneal 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, s...
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| Published in: | BMC genomics 2025-01, Vol.26 (1), p.48-11, Article 48 |
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| creator | Vo, Peter Imai-Leonard, Denise M Yang, Benjamin Briere, Andrew Shao, Andy Casanova, M Isabel Adams, David Amano, Takanori Amarie, Oana Berberovic, Zorana Bower, Lynette Braun, Robert Brown, Steve Burrill, Samantha Cho, Soo Young Clementson-Mobbs, Sharon D'Souza, Abigail Dickinson, Mary Eskandarian, Mohammad Flenniken, Ann M Fuchs, Helmut Gailus-Durner, Valerie Heaney, Jason Hérault, Yann Angelis, Martin Hrabe de Hsu, Chih-Wei Jin, Shundan Joynson, Russell Kang, Yeon Kyung Kim, Haerim Masuya, Hiroshi Meziane, Hamid Murray, Steve Nam, Ki-Hoan Noh, Hyuna Nutter, Lauryl M J Palkova, Marcela Prochazka, Jan Raishbrook, Miles Joseph Riet, Fabrice Ryan, Jennifer Salazar, Jason Seavey, Zachery Seavitt, John Richard Sedlacek, Radislav Selloum, Mohammed Seo, Kyoung Yul Seong, Je Kyung Shin, Hae-Sol Shiroishi, Toshihiko Stewart, Michelle Svenson, Karen Tamura, Masaru Tolentino, Heather Udensi, Uchechukwu Wells, Sara White, Jacqueline Willett, Amelia Wotton, Janine Wurst, Wolfgang Yoshiki, Atsushi Lanoue, Louise Lloyd, K C Kent Leonard, Brian C Roux, Michel J McKerlie, Colin Moshiri, Ala |
| description | Corneal 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.
8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P |
| doi_str_mv | 10.1186/s12864-025-11222-8 |
| format | article |
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8,707 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.
Analysis 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.
We 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.</description><identifier>ISSN: 1471-2164</identifier><identifier>EISSN: 1471-2164</identifier><identifier>DOI: 10.1186/s12864-025-11222-8</identifier><identifier>PMID: 39833678</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Abnormalities ; Analysis ; Animal research ; Animals ; Care and treatment ; Cornea ; Cornea - abnormalities ; Cornea - metabolism ; Cornea - pathology ; Corneal disease ; Corneal diseases ; Corneal Diseases - genetics ; Corneal Diseases - pathology ; Corneal Diseases - veterinary ; Corneal dysmorphologies ; Corneal dystrophies ; CRISPR ; Data analysis ; Diagnosis ; Epidemiology ; Eye diseases ; Eye disorders ; Genes ; Genetic aspects ; Genomes ; Genotype & phenotype ; Histopathology ; Humans ; Informatics ; Literature reviews ; Mice ; Mice, Knockout ; Mutation ; Ontology ; Pathology ; Pathophysiology ; Phenotype ; Phenotypes ; Phenotyping ; Protein interaction ; Protein-protein interactions ; Proteins ; RNA sequencing ; Signal transduction ; Statistical analysis ; Statistical methods ; Strings ; Therapeutic targets</subject><ispartof>BMC genomics, 2025-01, Vol.26 (1), p.48-11, Article 48</ispartof><rights>2025. The Author(s).</rights><rights>COPYRIGHT 2025 BioMed Central Ltd.</rights><rights>2025. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2025 2025</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c412t-f3229fc10b465c4b62b9d140f5a672df9e73cd08927a36071080170f1e2f9a423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744888/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3165435410?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39833678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vo, Peter</creatorcontrib><creatorcontrib>Imai-Leonard, Denise M</creatorcontrib><creatorcontrib>Yang, Benjamin</creatorcontrib><creatorcontrib>Briere, Andrew</creatorcontrib><creatorcontrib>Shao, Andy</creatorcontrib><creatorcontrib>Casanova, M Isabel</creatorcontrib><creatorcontrib>Adams, David</creatorcontrib><creatorcontrib>Amano, Takanori</creatorcontrib><creatorcontrib>Amarie, Oana</creatorcontrib><creatorcontrib>Berberovic, Zorana</creatorcontrib><creatorcontrib>Bower, Lynette</creatorcontrib><creatorcontrib>Braun, Robert</creatorcontrib><creatorcontrib>Brown, Steve</creatorcontrib><creatorcontrib>Burrill, Samantha</creatorcontrib><creatorcontrib>Cho, Soo Young</creatorcontrib><creatorcontrib>Clementson-Mobbs, Sharon</creatorcontrib><creatorcontrib>D'Souza, Abigail</creatorcontrib><creatorcontrib>Dickinson, Mary</creatorcontrib><creatorcontrib>Eskandarian, Mohammad</creatorcontrib><creatorcontrib>Flenniken, Ann M</creatorcontrib><creatorcontrib>Fuchs, Helmut</creatorcontrib><creatorcontrib>Gailus-Durner, Valerie</creatorcontrib><creatorcontrib>Heaney, Jason</creatorcontrib><creatorcontrib>Hérault, Yann</creatorcontrib><creatorcontrib>Angelis, Martin Hrabe de</creatorcontrib><creatorcontrib>Hsu, Chih-Wei</creatorcontrib><creatorcontrib>Jin, Shundan</creatorcontrib><creatorcontrib>Joynson, Russell</creatorcontrib><creatorcontrib>Kang, Yeon Kyung</creatorcontrib><creatorcontrib>Kim, Haerim</creatorcontrib><creatorcontrib>Masuya, Hiroshi</creatorcontrib><creatorcontrib>Meziane, Hamid</creatorcontrib><creatorcontrib>Murray, Steve</creatorcontrib><creatorcontrib>Nam, Ki-Hoan</creatorcontrib><creatorcontrib>Noh, Hyuna</creatorcontrib><creatorcontrib>Nutter, Lauryl M J</creatorcontrib><creatorcontrib>Palkova, Marcela</creatorcontrib><creatorcontrib>Prochazka, Jan</creatorcontrib><creatorcontrib>Raishbrook, Miles Joseph</creatorcontrib><creatorcontrib>Riet, Fabrice</creatorcontrib><creatorcontrib>Ryan, Jennifer</creatorcontrib><creatorcontrib>Salazar, Jason</creatorcontrib><creatorcontrib>Seavey, Zachery</creatorcontrib><creatorcontrib>Seavitt, John Richard</creatorcontrib><creatorcontrib>Sedlacek, Radislav</creatorcontrib><creatorcontrib>Selloum, Mohammed</creatorcontrib><creatorcontrib>Seo, Kyoung Yul</creatorcontrib><creatorcontrib>Seong, Je Kyung</creatorcontrib><creatorcontrib>Shin, Hae-Sol</creatorcontrib><creatorcontrib>Shiroishi, Toshihiko</creatorcontrib><creatorcontrib>Stewart, Michelle</creatorcontrib><creatorcontrib>Svenson, Karen</creatorcontrib><creatorcontrib>Tamura, Masaru</creatorcontrib><creatorcontrib>Tolentino, Heather</creatorcontrib><creatorcontrib>Udensi, Uchechukwu</creatorcontrib><creatorcontrib>Wells, Sara</creatorcontrib><creatorcontrib>White, Jacqueline</creatorcontrib><creatorcontrib>Willett, Amelia</creatorcontrib><creatorcontrib>Wotton, Janine</creatorcontrib><creatorcontrib>Wurst, Wolfgang</creatorcontrib><creatorcontrib>Yoshiki, Atsushi</creatorcontrib><creatorcontrib>Lanoue, Louise</creatorcontrib><creatorcontrib>Lloyd, K C Kent</creatorcontrib><creatorcontrib>Leonard, Brian C</creatorcontrib><creatorcontrib>Roux, Michel J</creatorcontrib><creatorcontrib>McKerlie, Colin</creatorcontrib><creatorcontrib>Moshiri, Ala</creatorcontrib><creatorcontrib>International Mouse Phenotyping Consortium</creatorcontrib><creatorcontrib>The International Mouse Phenotyping Consortium</creatorcontrib><title>Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes</title><title>BMC genomics</title><addtitle>BMC Genomics</addtitle><description>Corneal 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.
8,707 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.
Analysis 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.
We 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.</description><subject>Abnormalities</subject><subject>Analysis</subject><subject>Animal research</subject><subject>Animals</subject><subject>Care and treatment</subject><subject>Cornea</subject><subject>Cornea - abnormalities</subject><subject>Cornea - metabolism</subject><subject>Cornea - pathology</subject><subject>Corneal disease</subject><subject>Corneal diseases</subject><subject>Corneal Diseases - genetics</subject><subject>Corneal Diseases - pathology</subject><subject>Corneal Diseases - veterinary</subject><subject>Corneal dysmorphologies</subject><subject>Corneal dystrophies</subject><subject>CRISPR</subject><subject>Data analysis</subject><subject>Diagnosis</subject><subject>Epidemiology</subject><subject>Eye diseases</subject><subject>Eye disorders</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Informatics</subject><subject>Literature reviews</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mutation</subject><subject>Ontology</subject><subject>Pathology</subject><subject>Pathophysiology</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Phenotyping</subject><subject>Protein interaction</subject><subject>Protein-protein interactions</subject><subject>Proteins</subject><subject>RNA sequencing</subject><subject>Signal transduction</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Strings</subject><subject>Therapeutic 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ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes</title><author>Vo, Peter ; Imai-Leonard, Denise M ; Yang, Benjamin ; Briere, Andrew ; Shao, Andy ; Casanova, M Isabel ; Adams, David ; Amano, Takanori ; Amarie, Oana ; Berberovic, Zorana ; Bower, Lynette ; Braun, Robert ; Brown, Steve ; Burrill, Samantha ; Cho, Soo Young ; Clementson-Mobbs, Sharon ; D'Souza, Abigail ; Dickinson, Mary ; Eskandarian, Mohammad ; Flenniken, Ann M ; Fuchs, Helmut ; Gailus-Durner, Valerie ; Heaney, Jason ; Hérault, Yann ; Angelis, Martin Hrabe de ; Hsu, Chih-Wei ; Jin, Shundan ; Joynson, Russell ; Kang, Yeon Kyung ; Kim, Haerim ; Masuya, Hiroshi ; Meziane, Hamid ; Murray, Steve ; Nam, Ki-Hoan ; Noh, Hyuna ; Nutter, Lauryl M J ; Palkova, Marcela ; Prochazka, Jan ; Raishbrook, Miles Joseph ; Riet, Fabrice ; Ryan, Jennifer ; Salazar, Jason ; Seavey, Zachery ; Seavitt, John Richard ; Sedlacek, Radislav ; Selloum, Mohammed ; Seo, Kyoung Yul ; Seong, Je Kyung ; Shin, Hae-Sol ; Shiroishi, Toshihiko ; Stewart, Michelle ; Svenson, Karen ; Tamura, Masaru ; Tolentino, Heather ; Udensi, Uchechukwu ; Wells, Sara ; White, Jacqueline ; Willett, Amelia ; Wotton, Janine ; Wurst, Wolfgang ; Yoshiki, Atsushi ; Lanoue, Louise ; Lloyd, K C Kent ; Leonard, Brian C ; Roux, Michel J ; McKerlie, Colin ; Moshiri, Ala</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-f3229fc10b465c4b62b9d140f5a672df9e73cd08927a36071080170f1e2f9a423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Abnormalities</topic><topic>Analysis</topic><topic>Animal research</topic><topic>Animals</topic><topic>Care and treatment</topic><topic>Cornea</topic><topic>Cornea - abnormalities</topic><topic>Cornea - metabolism</topic><topic>Cornea - pathology</topic><topic>Corneal disease</topic><topic>Corneal diseases</topic><topic>Corneal Diseases - genetics</topic><topic>Corneal Diseases - pathology</topic><topic>Corneal Diseases - veterinary</topic><topic>Corneal dysmorphologies</topic><topic>Corneal dystrophies</topic><topic>CRISPR</topic><topic>Data analysis</topic><topic>Diagnosis</topic><topic>Epidemiology</topic><topic>Eye diseases</topic><topic>Eye disorders</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Histopathology</topic><topic>Humans</topic><topic>Informatics</topic><topic>Literature reviews</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mutation</topic><topic>Ontology</topic><topic>Pathology</topic><topic>Pathophysiology</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Phenotyping</topic><topic>Protein interaction</topic><topic>Protein-protein interactions</topic><topic>Proteins</topic><topic>RNA sequencing</topic><topic>Signal transduction</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Strings</topic><topic>Therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vo, Peter</creatorcontrib><creatorcontrib>Imai-Leonard, Denise M</creatorcontrib><creatorcontrib>Yang, Benjamin</creatorcontrib><creatorcontrib>Briere, Andrew</creatorcontrib><creatorcontrib>Shao, Andy</creatorcontrib><creatorcontrib>Casanova, M Isabel</creatorcontrib><creatorcontrib>Adams, David</creatorcontrib><creatorcontrib>Amano, Takanori</creatorcontrib><creatorcontrib>Amarie, Oana</creatorcontrib><creatorcontrib>Berberovic, Zorana</creatorcontrib><creatorcontrib>Bower, Lynette</creatorcontrib><creatorcontrib>Braun, Robert</creatorcontrib><creatorcontrib>Brown, Steve</creatorcontrib><creatorcontrib>Burrill, Samantha</creatorcontrib><creatorcontrib>Cho, Soo Young</creatorcontrib><creatorcontrib>Clementson-Mobbs, Sharon</creatorcontrib><creatorcontrib>D'Souza, Abigail</creatorcontrib><creatorcontrib>Dickinson, Mary</creatorcontrib><creatorcontrib>Eskandarian, Mohammad</creatorcontrib><creatorcontrib>Flenniken, Ann M</creatorcontrib><creatorcontrib>Fuchs, Helmut</creatorcontrib><creatorcontrib>Gailus-Durner, Valerie</creatorcontrib><creatorcontrib>Heaney, Jason</creatorcontrib><creatorcontrib>Hérault, Yann</creatorcontrib><creatorcontrib>Angelis, Martin Hrabe de</creatorcontrib><creatorcontrib>Hsu, Chih-Wei</creatorcontrib><creatorcontrib>Jin, Shundan</creatorcontrib><creatorcontrib>Joynson, Russell</creatorcontrib><creatorcontrib>Kang, Yeon Kyung</creatorcontrib><creatorcontrib>Kim, Haerim</creatorcontrib><creatorcontrib>Masuya, Hiroshi</creatorcontrib><creatorcontrib>Meziane, Hamid</creatorcontrib><creatorcontrib>Murray, Steve</creatorcontrib><creatorcontrib>Nam, Ki-Hoan</creatorcontrib><creatorcontrib>Noh, Hyuna</creatorcontrib><creatorcontrib>Nutter, Lauryl M J</creatorcontrib><creatorcontrib>Palkova, Marcela</creatorcontrib><creatorcontrib>Prochazka, Jan</creatorcontrib><creatorcontrib>Raishbrook, Miles Joseph</creatorcontrib><creatorcontrib>Riet, Fabrice</creatorcontrib><creatorcontrib>Ryan, Jennifer</creatorcontrib><creatorcontrib>Salazar, Jason</creatorcontrib><creatorcontrib>Seavey, Zachery</creatorcontrib><creatorcontrib>Seavitt, John Richard</creatorcontrib><creatorcontrib>Sedlacek, Radislav</creatorcontrib><creatorcontrib>Selloum, Mohammed</creatorcontrib><creatorcontrib>Seo, Kyoung Yul</creatorcontrib><creatorcontrib>Seong, Je Kyung</creatorcontrib><creatorcontrib>Shin, Hae-Sol</creatorcontrib><creatorcontrib>Shiroishi, Toshihiko</creatorcontrib><creatorcontrib>Stewart, Michelle</creatorcontrib><creatorcontrib>Svenson, Karen</creatorcontrib><creatorcontrib>Tamura, Masaru</creatorcontrib><creatorcontrib>Tolentino, Heather</creatorcontrib><creatorcontrib>Udensi, Uchechukwu</creatorcontrib><creatorcontrib>Wells, Sara</creatorcontrib><creatorcontrib>White, Jacqueline</creatorcontrib><creatorcontrib>Willett, Amelia</creatorcontrib><creatorcontrib>Wotton, Janine</creatorcontrib><creatorcontrib>Wurst, Wolfgang</creatorcontrib><creatorcontrib>Yoshiki, Atsushi</creatorcontrib><creatorcontrib>Lanoue, Louise</creatorcontrib><creatorcontrib>Lloyd, K C Kent</creatorcontrib><creatorcontrib>Leonard, Brian C</creatorcontrib><creatorcontrib>Roux, Michel J</creatorcontrib><creatorcontrib>McKerlie, Colin</creatorcontrib><creatorcontrib>Moshiri, Ala</creatorcontrib><creatorcontrib>International Mouse Phenotyping Consortium</creatorcontrib><creatorcontrib>The International Mouse Phenotyping Consortium</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue 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Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>BMC genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vo, Peter</au><au>Imai-Leonard, Denise M</au><au>Yang, Benjamin</au><au>Briere, Andrew</au><au>Shao, Andy</au><au>Casanova, M Isabel</au><au>Adams, David</au><au>Amano, Takanori</au><au>Amarie, Oana</au><au>Berberovic, Zorana</au><au>Bower, Lynette</au><au>Braun, Robert</au><au>Brown, Steve</au><au>Burrill, Samantha</au><au>Cho, Soo Young</au><au>Clementson-Mobbs, Sharon</au><au>D'Souza, Abigail</au><au>Dickinson, Mary</au><au>Eskandarian, Mohammad</au><au>Flenniken, Ann M</au><au>Fuchs, Helmut</au><au>Gailus-Durner, Valerie</au><au>Heaney, Jason</au><au>Hérault, Yann</au><au>Angelis, Martin Hrabe de</au><au>Hsu, Chih-Wei</au><au>Jin, Shundan</au><au>Joynson, Russell</au><au>Kang, Yeon Kyung</au><au>Kim, Haerim</au><au>Masuya, Hiroshi</au><au>Meziane, Hamid</au><au>Murray, Steve</au><au>Nam, Ki-Hoan</au><au>Noh, Hyuna</au><au>Nutter, Lauryl M J</au><au>Palkova, Marcela</au><au>Prochazka, Jan</au><au>Raishbrook, Miles Joseph</au><au>Riet, Fabrice</au><au>Ryan, Jennifer</au><au>Salazar, Jason</au><au>Seavey, Zachery</au><au>Seavitt, John Richard</au><au>Sedlacek, Radislav</au><au>Selloum, Mohammed</au><au>Seo, Kyoung Yul</au><au>Seong, Je Kyung</au><au>Shin, Hae-Sol</au><au>Shiroishi, Toshihiko</au><au>Stewart, Michelle</au><au>Svenson, Karen</au><au>Tamura, Masaru</au><au>Tolentino, Heather</au><au>Udensi, Uchechukwu</au><au>Wells, Sara</au><au>White, Jacqueline</au><au>Willett, Amelia</au><au>Wotton, Janine</au><au>Wurst, Wolfgang</au><au>Yoshiki, Atsushi</au><au>Lanoue, Louise</au><au>Lloyd, K C Kent</au><au>Leonard, Brian C</au><au>Roux, Michel J</au><au>McKerlie, Colin</au><au>Moshiri, Ala</au><aucorp>International Mouse Phenotyping Consortium</aucorp><aucorp>The International Mouse Phenotyping Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes</atitle><jtitle>BMC genomics</jtitle><addtitle>BMC Genomics</addtitle><date>2025-01-20</date><risdate>2025</risdate><volume>26</volume><issue>1</issue><spage>48</spage><epage>11</epage><pages>48-11</pages><artnum>48</artnum><issn>1471-2164</issn><eissn>1471-2164</eissn><abstract>Corneal 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.
8,707 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.
Analysis 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.
We 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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>39833678</pmid><doi>10.1186/s12864-025-11222-8</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1471-2164 |
| ispartof | BMC genomics, 2025-01, Vol.26 (1), p.48-11, Article 48 |
| issn | 1471-2164 1471-2164 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_7346cc15ec8248fdb069983714a55d83 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | Abnormalities Analysis Animal research Animals Care and treatment Cornea Cornea - abnormalities Cornea - metabolism Cornea - pathology Corneal disease Corneal diseases Corneal Diseases - genetics Corneal Diseases - pathology Corneal Diseases - veterinary Corneal dysmorphologies Corneal dystrophies CRISPR Data analysis Diagnosis Epidemiology Eye diseases Eye disorders Genes Genetic aspects Genomes Genotype & phenotype Histopathology Humans Informatics Literature reviews Mice Mice, Knockout Mutation Ontology Pathology Pathophysiology Phenotype Phenotypes Phenotyping Protein interaction Protein-protein interactions Proteins RNA sequencing Signal transduction Statistical analysis Statistical methods Strings Therapeutic targets |
| title | Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes |
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