Document Type

Article

Publication Date

1-30-2022

Publication Title

Int J Mol Sci

Keywords

JMG, Animals, Breeding, Disease Models, Animal, Epistasis, Genetic, Eye Proteins, Homozygote, Membrane Proteins, Mice, Mutation, Ophthalmoscopy, Phenotype, Receptors, Adiponectin, Retinal Degeneration

JAX Source

Int J Mol Sci 2022 Jan 30; 23(3):1615

Volume

23

Issue

3

ISSN

1422-0067

PMID

35163536

DOI

https://doi.org/10.3390/ijms23031615

Grant

EY011996, CA034196

Abstract

Adipor1tm1Dgen and Mfrprd6 mutant mice share similar eye disease characteristics. Previously, studies established a functional relationship of ADIPOR1 and MFRP proteins in maintaining retinal lipidome homeostasis and visual function. However, the independent and/or interactive contribution of both genes to similar disease phenotypes, including fundus spots, decreased axial length, and photoreceptor degeneration has yet to be examined. We performed a gene-interaction study where homozygous Adipor1tm1Dgen and Mfrprd6 mice were bred together and the resulting doubly heterozygous F1 offspring were intercrossed to produce 210 F2 progeny. Four-month-old mice from all nine genotypic combinations obtained in the F2 generation were assessed for white spots by fundus photo documentation, for axial length by caliper measurements, and for photoreceptor degeneration by histology. Two-way factorial ANOVA was performed to study individual as well as gene interaction effects on each phenotype. Here, we report the first observation of reduced axial length in Adipor1tmlDgen homozygotes. We show that while Adipor1 and Mfrp interact to affect spotting and degeneration, they act independently to control axial length, highlighting the complex functional association between these two genes. Further examination of the molecular basis of this interaction may help in uncovering mechanisms by which these genes perturb ocular homeostasis.

Comments

The authors thank the JAX Scientific Research Services, including the Histological and Transgenic Genotyping Services for genotyping mice strains, Melissa Berry for assistance with nomenclature, Jim Peterson for designing the algorithm for PR nuclei counting, and Mark P. Krebs for his useful discussions.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

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