Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 2;66(6):64.
doi: 10.1167/iovs.66.6.64.

Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes

Abraham Hang  1 , Andy Shao  1 , Michael Shea  1 , Michel J Roux  2 , Denise M Imai-Leonard  3 , David J Adams  4 , Takanori Amano  5 , Oana V Amarie  6 , Zorana Berberovic  7 , Raphaël Bour  8 , Lynette Bower  9 , Brian C Leonard  10 , Steve D Brown  11 , Soo Young Cho  12 , Sharon Clementson-Mobbs  13 , Abigail J D'Souza  7 , Mary Dickinson  14 , Mohammad Eskandarian  7 , Ann M Flenniken  7 , Helmut Fuchs  6 , Valerie Gailus-Durner  6 , Jason Heaney  15 , Yann Hérault  8 , Martin Hrabe de Angelis  6   16   17 , Chih-Wei Hsu  14 , Shundan Jin  5 , Russell Joynson  13 , Yeon Kyung Kang  18 , Haerim Kim  19 , Hiroshi Masuya  5 , Ki-Hoan Nam  19 , Hyuna Noh  18 , Lauryl M J Nutter  20 , Marcela Palkova  21 , Jan Prochazka  21 , Miles Joseph Raishbrook  21 , Fabrice Riet  8 , Jason Salazar  9 , John Richard Seavitt  15 , Radislav Sedlacek  21 , Mohammed Selloum  8 , Kyoung Yul Seo  22 , Je Kyung Seong  23 , Hae-Sol Shin  22 , Toshihiko Shiroishi  5 , Tania Sorg  8 , Michelle Stewart  13 , Masaru Tamura  5 , Heather Tolentino  9 , Uchechukwu Udensi  14 , Sara Wells  13 , Wolfgang Wurst  24   25   26   27   28 , Atsushi Yoshiki  5 , Hamid Meziane  8 , Glenn Yiu  1 , Paul A Sieving  1 , Louise Lanoue  9 , K C Kent Lloyd  9   29 , Colin McKerlie  20   30 , Ala Moshiri  1 ; International Mouse Phenotyping Consortium (IMPC)
Affiliations

Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes

Abraham Hang et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.

Methods: 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).

Results: 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.

Conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

Disclosure: A. Hang, None; A. Shao, None; M. Shea, None; M.J. Roux, None; D.M. Imai-Leonard, None; D.J. Adams, None; T. Amano, None; O.V. Amarie, None; Z. Berberovic, None; R. Bour, None; L. Bower, None; B.C. Leonard, None; S.D. Brown, None; S.Y. Cho, None; S. Clementson-Mobbs, None; A.J. D'Souza, None; M. Dickinson, None; M. Eskandarian, None; A.M. Flenniken, None; H. Fuchs, None; V. Gailus-Durner, None; J. Heaney, None; Y. Hérault, None; M. Hrabe de Angelis, None; C.-W. Hsu, None; S. Jin, None; R. Joynson, None; Y.K. Kang, None; H. Kim, None; H. Masuya, None; K.-H. Nam, None; H. Noh, None; L.M.J. Nutter, None; M. Palkova, None; J. Prochazka, None; M.J. Raishbrook, None; F. Riet, None; J. Salazar, None; J.R. Seavitt, None; R. Sedlacek, None; M. Selloum, None; K.Y. Seo, None; J.K. Seong, None; H.-S. Shin, None; T. Shiroishi, None; T. Sorg, None; M. Stewart, None; M. Tamura, None; H. Tolentino, None; U. Udensi, None; S. Wells, None; W. Wurst, None; A. Yoshiki, None; H. Meziane, None; G. Yiu, None; P.A. Sieving, None; L. Lanoue, None; K.C.K. Lloyd, None; C. McKerlie, None; A. Moshiri, None

Figures

Figure 1.
Figure 1.
Fundus photograph examples of knockout lines with retinal abnormalities. (A) Tat homozygote at 75 weeks with pigmentary changes throughout the fundus. (B) Atp8b1 homozygote at 58 weeks with numerous yellow spots and a lesion below the optic nerve (arrow). (C) Wild-type C57BL/6NCrl at 58 weeks for comparison. Some yellow spots are seen (arrow) consistent with background rd8 mutation. (D) Wild-type C57BL/6NCrl at 9 weeks.
Figure 2.
Figure 2.
Histological example of knockout line with retinal abnormalities. (A) Atp8b1 homozygote knockout at 59 weeks demonstrating numerous cells present in the outer plexiform layer (yellow arrows). (B) Wild-type at 59 weeks showing normal anatomy of the retina.
Figure 3.
Figure 3.
STRING analysis of protein–protein interactions. (A) Interaction between MT1 candidate gene orthologs (purple). (B) Interaction between GNB4 (1) (purple) with RetNet database genes (green). (C) Interaction between TAT (2) and SORL1 (3) candidate genes (purple) with AMD GWAS genes (blue). Organism set to Homo sapiens (settings: network type = full STRING network, selectivity of interactors = 0.7). Nodes corresponding to genes for which there were PubMed reports of implication in retinal physiology or pathology in human, mouse or both are circled respectively in gray, blue, or red.
Figure 4.
Figure 4.
Molecular pathways of 20 candidate genes using the PANTHER tool, with each slice representing the proportion of the specific molecular pathway among the 20 genes.
See this image and copyright information in PMC

References

    1. Bessant DA, Ali RR, Bhattacharya SS. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev. 2001; 11: 307–316. - PubMed
    1. Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010; 29: 335–375. - PubMed
    1. Pontikos N, Arno G, Jurkute N, et al.. Genetic basis of inherited retinal disease in a molecularly characterized cohort of more Than 3000 families from the United Kingdom. Ophthalmology. 2020; 127: 1384–1394. - PMC - PubMed
    1. Goetz KE, Reeves MJ, Gagadam S, et al.. Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network. Am J Med Genet C Semin Med Genet. 2020; 184: 828–837. - PMC - PubMed
    1. Mustafi D, Hisama FM, Huey J, Chao JR. The current state of genetic testing platforms for inherited retinal diseases. Ophthalmol Retina. 2022; 6: 702–710. - PMC - PubMed