System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ppublish 2 citations

PubMed: 39151208 DOI: 10.1016/j.visres.2024.108464

Minimal phenotypes in transgenic mice with the human LOXL1/LOXL1-AS1 locus associated with exfoliation glaucoma.

Vision Res 223:108464

Authors: Kacie J Meyer, Hannah E Mercer, Ben R Roos, John H Fingert, Michael G Anderson

Affiliations

  • Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States; Institute for Vision Research, University of Iowa, Iowa City, IA, United States.
  • Institute for Vision Research, University of Iowa, Iowa City, IA, United States; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, United States.
  • Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States; Institute for Vision Research, University of Iowa, Iowa City, IA, United States; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, United States; Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, Iowa City, IA, United States.

Abstract

Exfoliation syndrome is a leading cause of secondary glaucoma worldwide. Among the risk-factors for exfoliation syndrome and exfoliation glaucoma that have been investigated, a genetic association with 15q24.1 is among the most striking. The leading candidates for the causal gene at this locus are LOXL1 and/or LOXL1-AS1, but studies have not yet coalesced in establishing, or ruling out, either candidate. Here, we contribute to studies of the 15q24.1 locus by making a partially humanized mouse model in which 166 kb of human genomic DNA from the 15q24.1 locus was introduced into the mouse genome via BAC transgenesis (B6-Tg(RP11-71M11)Andm). Transgenic expression of human genes in the BAC was only detectable for LOXL1-AS1. One cohort of 34 mice (21 experimental hemizygotes and 13 non-carrier control littermates) was assessed by slit-lamp exams and SD-OCT imaging at early (1-2 months) and mid (4-5 months) time points; fundus exams were performed at 5 months of age. A second smaller cohort (3 hemizygotes) were aged extensively (>12 months) to screen for overt abnormalities. Across all genotypes and ages, 136 slit-lamp exams, 128 SD-OCT exams, and 42 fundus exams detected no overt indices of exfoliation syndrome. Quantitatively, small, but statistically significant, age-related declines in ganglion cell complex thickness and total retinal thickness were detected in the hemizygotes at 4 months of age. Overall, this study demonstrates complexity in gene regulation from the 15q24.1 locus and suggests that LOXL1-AS1 is unlikely to be a monogenic cause of exfoliation syndrome but may contribute to glaucomatous retinal damage.

MeSH

Genes, Vision, Ocular, Ophthalmology, Phenotype, Hemizygote, Glaucoma, Retinaldehyde, Exfoliation Syndrome

Cited by