Disruption of circadian intraocular pressure fluctuations in mice by the Lyst beige-J mutation

Colleen M. McDowell; Laura M. Dutca; Stewart Thompson; Megan Riker; Adam Hedberg-Buenz; Kacie J. Meyer; Michael G. Anderson

doi:10.1016/j.exer.2025.110266

Back

Disruption of circadian intraocular pressure fluctuations in mice by the Lyst beige-J mutation

Journal article

Peer reviewed

Disruption of circadian intraocular pressure fluctuations in mice by the Lyst beige-J mutation

Colleen M. McDowell, Laura M. Dutca, Stewart Thompson, Megan Riker, Adam Hedberg-Buenz, Kacie J. Meyer and Michael G. Anderson

Experimental eye research, Vol.252, 110266

01/31/2025

DOI: 10.1016/j.exer.2025.110266

PMCID: PMC11864214

PMID: 39894294

View Online

Abstract

Intraocular pressure (IOP) follows a circadian rhythm. In both humans and mice, IOP is normally slightly elevated at night during the dark phase of the light cycle. In studying a strain of mice for possible indices of glaucoma, we incidentally discovered that C57BL/6J mice homozygous for the beige-J mutation of the Lyst gene lack a circadian fluctuation in IOP. Instead of having an elevated dark phase IOP, homozygotes exhibit a uniform IOP characteristic for light period values of C57BL/6J mice. The beige-J mutation results from deletion of a single isoleucine amino acid in the LYST WD40 motif likely to influence protein-protein interactions. Based on the literature, we hypothesized that CSNK2B (casein kinase 2, beta polypeptide) might be a relevant interacting protein, which we confirmed with a pulldown assay as a binding partner of wild-type, but not beige-J encoding, LYST protein. Treating wild-type mice with 4,5,6,7-tetrabromobenzotriazole (TBB), a casein kinase 2 inhibitor, recapitulated the beige-J mutant phenotype in preventing a rise in IOP during the dark period. Together, these results identify Lyst beige-J mice as a new strain for studying circadian IOP regulation and point to casein kinase 2 as a key molecule of interest. •Mice homozygous for the Lyst beige-J mutation lack the characteristic rise in IOP during the dark phase•Casein kinase 2 is implicated as a key molecule to circadian IOP.•Casein kinase 2 inhibitors may have relevance to glaucoma therapy.

Animal Models

Circadian

CSNK2B

Intraocular pressure

LYST

TBB

Details

Title: Subtitle: Disruption of circadian intraocular pressure fluctuations in mice by the Lyst beige-J mutation
Creators: Colleen M. McDowell - University of Iowa
Laura M. Dutca - University of Iowa
Stewart Thompson - University of Iowa
Megan Riker - University of Iowa
Adam Hedberg-Buenz - University of Iowa
Kacie J. Meyer - University of Iowa
Michael G. Anderson - University of Iowa
Resource Type: Journal article
Publication Details: Experimental eye research, Vol.252, 110266
DOI: 10.1016/j.exer.2025.110266
PMID: 39894294
PMCID: PMC11864214
NLM abbreviation: Exp Eye Res
ISSN: 0014-4835
eISSN: 1096-0007
Publisher: Elsevier Ltd
Grant note: NIH/NEI: EY017673, EY034492, EY026529 US Dept. of Veterans Affairs/RR D: I01RX001481, IK2 RX002003 NIH/NEI Center Support: P30EY025580
This work was supported by grants from the NIH/NEI (EY017673, MGA; EY034492, MGA) and US Dept. of Veterans Affairs/RR & D (I01RX001481, MGA; IK2 RX002003, LD) . CMM is currently supported by NIH/NEI grant EY026529. We also acknowledge NIH/NEI Center Support from Grant P30EY025580 to the University of Iowa. The contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. Government.
Language: English
Date published: 01/31/2025
Academic Unit: Molecular Physiology and Biophysics; The University of Iowa Institute for Vision Research; Ophthalmology and Visual Sciences
Record Identifier: 9984786281702771

Metrics

9 Record Views

See more details