Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas

Abstract

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8–12 weeks (young) or 45–55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

GWAS Hits for Bilateral Convergent Strabismus with Exophthalmos in Holstein Cattle Using Imputed Sequence Level Genotypes

“…Despite the fact that Mrp4 -deficient mice are born viable and do not show any obvious anomalies, it is known that they express abnormal reactions to various types of stress including retinal dystrophy [ 29 ]. Therefore, it was recently stated that MRP4 may play a role in the process of aging [ 30 ]. In light of the obtained GWAS results, one could therefore speculate that variants in the bovine ABCC4 might have an impact on the development of BCSE in cattle, an anomaly that continuously progresses during aging.…”