Hang Abraham, Shao Andy, Shea Michael, Roux Michel J, Imai-Leonard Denise M, Adams David J, Amano Takanori, Amarie Oana V, Berberovic Zorana, Bour Raphaël, Bower Lynette, Leonard Brian C, Brown Steve D, Cho Soo Young, Clementson-Mobbs Sharon, D'Souza Abigail J, Dickinson Mary, Eskandarian Mohammad, Flenniken Ann M, Fuchs Helmut, Gailus-Durner Valerie, Heaney Jason, Hérault Yann, Hrabe de Angelis Martin, Hsu Chih-Wei, Jin Shundan, Joynson Russell, Kang Yeon Kyung, Kim Haerim, Masuya Hiroshi, Nam Ki-Hoan, Noh Hyuna, Nutter Lauryl M J, Palkova Marcela, Prochazka Jan, Raishbrook Miles Joseph, Riet Fabrice, Salazar Jason, Seavitt John Richard, Sedlacek Radislav, Selloum Mohammed, Seo Kyoung Yul, Seong Je Kyung, Shin Hae-Sol, Shiroishi Toshihiko, Sorg Tania, Stewart Michelle, Tamura Masaru, Tolentino Heather, Udensi Uchechukwu, Wells Sara, Wurst Wolfgang, Yoshiki Atsushi, Meziane Hamid, Yiu Glenn C, Sieving Paul A, Lanoue Louise, Lloyd K C Kent, McKerlie Colin, Moshiri Ala
Department of Ophthalmology and Vision Science, University of California Davis Eye Center, Sacramento, California, United States.
Université de Strasbourg, CNRS (UMR 7104), Inserm (UMR-S 1258), Illkirch, France.
Invest Ophthalmol Vis Sci. 2025 Jun 2;66(6):64. doi: 10.1167/iovs.66.6.64.
Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.
The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG).
Screening of 587 late-adult mouse genes yielded 12 with abnormal retinal phenotypes, which corresponded to 20 human orthologs. Three of the 12 mouse genes and two of the 20 human orthologs were previously implicated in retinal pathology or physiology in a literature review. Although all of the genes demonstrated retinal pathology when deleted from the mouse genome, most do not have established roles in human retinal disease. Furthermore, human protein-protein analysis and biological pathway analysis yielded only a few relationships between the candidate gene list and that of known IRD and AMD genes, suggesting they may represent novel retinal functions.
We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene candidates for late-onset retinal disease.
分析具有成年晚期视网膜病理表型的基因敲除小鼠的表型数据，以鉴定与成年发病型视网膜疾病发生相关的基因。
在国际小鼠表型分析联盟（IMPC）数据库中查询与成年晚期基因敲除小鼠品系（出生后49 - 80周龄）中视网膜异常表型相关的基因。我们鉴定了人类直系同源基因，并使用检索相互作用基因/蛋白质的搜索工具（STRING）、盘状单细胞眼分析平台（PLAE）、通过进化关系进行蛋白质分析（PANTHER）和京都基因与基因组百科全书（KEGG），对已知的遗传性视网膜疾病（IRD）和年龄相关性黄斑变性（AMD）基因进行蛋白质 - 蛋白质分析和生物途径分析。
对587个成年晚期小鼠基因进行筛选，得到12个具有视网膜异常表型的基因，它们对应于20个人类直系同源基因。在文献综述中，12个小鼠基因中的3个和20个人类直系同源基因中的2个先前已涉及视网膜病理或生理过程。尽管所有这些基因从小鼠基因组中缺失时均表现出视网膜病理，但大多数在人类视网膜疾病中尚未明确其作用。此外，人类蛋白质 - 蛋白质分析和生物途径分析在候选基因列表与已知IRD和AMD基因列表之间仅产生了少数关联，表明它们可能代表了新的视网膜功能。
我们鉴定出12个具有显著成年晚期视网膜异常病理的小鼠基因，其中8个此前在小鼠或人类视网膜生理或病理过程中均未涉及。这些基因可作为迟发性视网膜疾病新的视网膜疾病基因候选者。
