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研究発表を行った学会;Keystone Symposia Intra- and Intercellular Mechanisms of Aging
2020年2月9日〜13日(Vancouver, BC, Canada)
タイトル; Functional diversification of duplicated mineralocorticoid receptors in naked mole-rat (Heterocephalus glaber).
発表者;岡 香織氏
(熊本大学 大学院生命科学研究部 老化・健康長寿学講座)
The naked mole-rat (NMR, Heterocephalus glaber) is the longest-lived rodent, with a maximum lifespan exceeding 30 years. These small rodents inhabit subterranean burrows in the dry, arid savannas of north-east Africa, and thus have no access to free water. Therefore, we hypothesized that NMRs have evolved adaptive mechanisms for maintaining body fluid balance to withstand an extreme environment. The renin-angiotensin-aldosterone system is one of the major hormonal systems that regulate fluid balance and associated with the pathogenesis of vascular disease. A previous report has shown that the NMRs exhibit a moderate kidney concentrating ability, however, the molecular characterization of renin-angiotensin-aldosterone system genes remains completely unexplored. Here, we show that the mineralocorticoid receptor (MR) gene, which mediates aldosterone effects on fluid homeostasis, is duplicated and functionally differentiated in NMRs. Sequence analysis identified two putative MR genes in NMRs.One designated as MR1 exhibited high amino acid sequence identity to the mouse ortholog. The other was truncated due to a premature stop codon and a partial gene duplication, resulting in the loss of the domain required for DNA- and ligand-binding, and named MR2. Transcriptome analysis of public data indicated that MR1 was highly expressed in the kidney and nervous system, whereas MR2 was highly expressed in several tissues, including the thyroid and gonads. Using cell-based luciferase reporter assays, MR1 proteins displayed corticosteroid-dependent activation of transcription from keto-steroid hormone-responsive, murine mammary tumor virus promoters. Although MR2 alone had no transcriptional activation potential reflected by its domain structure, co-transfection with MR1 increased its transcriptional activity. Our results suggest that MR2, specifically acquired in NMRs, may function as a novel regulator of the activity of MR1 to properly control the fluid homeostasis and to protect their body from vascular diseases.

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