Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 3 February 2021 / Approved: 4 February 2021 / Online: 4 February 2021 (10:58:06 CET)

How to cite: Kim, K.W.; Kusuhara, S.; Katsuyama-Yoshikawa, A.; Nobuyoshi, S.; Kitamura, M.; Mori, S.; Sotani, N.; Ueda, K.; Matsumiya, W.; Miki, A.; Kurimoto, T.; Imai, H.; Nakamura, M. Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retina. Preprints 2021, 2021020132 (doi: 10.20944/preprints202102.0132.v1). Kim, K.W.; Kusuhara, S.; Katsuyama-Yoshikawa, A.; Nobuyoshi, S.; Kitamura, M.; Mori, S.; Sotani, N.; Ueda, K.; Matsumiya, W.; Miki, A.; Kurimoto, T.; Imai, H.; Nakamura, M. Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retina. Preprints 2021, 2021020132 (doi: 10.20944/preprints202102.0132.v1).

Abstract

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter that is responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the co-effects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of the mouse retina. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same condition to 8–12 wk (young) or 45–55 wk (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to that from aged WT mice, and subsequence gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision, and transcellular barrier function 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 4 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.

Subject Areas

multidrug resistance protein 4; ATP-binding cassette (ABC) transporters; aging; retina; mouse; electroretinogram

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