Document Type
Article
Publication Date
9-1-2025
Original Citation
Wotton J,
Krebs MP,
Sangermano R,
Wong J,
Smith C,
Willett A,
Howell D,
Jones A,
Witmeyer C,
Lowy J,
McFarland M,
Murray S,
Braun R,
Nishina PM,
Pierce E,
Place E,
Bujakowska K,
Peachey N,
White J.
Identifying genetic determinants of outer retinal function in mice using a large-scale gene-targeted screen. PLoS Genet. 2025;21(9):e1011886.
Keywords
JMG, JCA, Animals, Electroretinography, Mice, Retina, Humans, Retinal Degeneration, Mice, Knockout, Nerve Tissue Proteins
JAX Source
PLoS Genet. 2025;21(9):e1011886.
ISSN
1553-7404
PMID
41021661
DOI
https://doi.org/10.1371/journal.pgen.1011886
Grant
JKW, REB, and SAM received grant number UM1OD023222, in the form of the Ocular Supplement grant 3UM1OD023222- 08S1 from the Office of the Director of the National Institutes of Health (https://www. nih.gov/grants-funding). Authors from the Massachusetts Eye and Ear Institute (MEEI) received funding as follows from the National Eye Institute (https://www.nei.nih.gov/): EAP received grant number R01EY012910; KMB and EAP received grant number R01EY035717; MEEI Core support was provided by P30EY014104. PMN received grant number R01EY027305 from the National Eye Institute (https://www.nei.nih.gov/).
Abstract
Electroretinography (ERG) provides a noninvasive functional measure of multiple cell types of the outer retina. We conducted an ERG-based screen of 530 single-gene knockout mouse strains generated as part of the International Mouse Phenotyping Consortium, representing 2.5% of all protein-coding genes, to identify genetic variants affecting retinal function. We identified 30 strains with significantly altered ERG amplitudes. Two of the genes identified, Cfap418 and Syne2, have been previously reported with outer retinal dysfunction, thereby serving as internal controls that validate our screening protocol. Of the remaining 28 genes newly associated with altered retinal function, the majority lacked a contemporaneous histopathology correlate, highlighting the importance of ERG in early detection of functional abnormalities. A rare homozygous missense variant in FCHSD2, the human orthologue of one of the 28 genes identified, was found in a patient presenting with retinal degeneration that lacked a molecular diagnosis. This report represents a useful resource for future investigations into the molecular mechanisms driving inherited retinal diseases and demonstrates the power of large-scale ERG screening in identifying novel genetic determinants of retinal function.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.