Diversification of mineralocorticoid receptor genes in a subterranean rodent, the naked mole-rat

in Journal of Molecular Endocrinology
Authors:
Kaori Oka Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

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https://orcid.org/0000-0002-8753-1685
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Hidemasa Bono Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan

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https://orcid.org/0000-0003-4413-0651
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Asato Kuroiwa Division of Reproductive and Developmental Biology, Department of Biological Sciences, Faculty of Science, Hokkaido University, Sapporo, Japan

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Shusuke Fujioka Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

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Atsushi Shimizu Division of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical University, Shiwa, Japan

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Yoshinao Katsu Division of Reproductive and Developmental Biology, Department of Biological Sciences, Faculty of Science, Hokkaido University, Sapporo, Japan

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Kyoko Miura Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, Japan

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Correspondence should be addressed to K Oka or K Miura: okaori@kumamoto-u.ac.jp or miurak@kumamoto-u.ac.jp

*(K Miura is the lead contact)

DOI:
https://doi.org/10.1530/JME-20-0325
Volume/Issue:
Volume 66: Issue 4
Article Type:
Research Article
Page Range:
299–311
Online Publication Date:
11 May 2021
Copyright:
© Society for Endocrinology 2021
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Naked mole-rats (Heterocephalus glaber) inhabit subterranean burrows in savannas and are, thus, unable to access free water. To identify their mechanism of osmoregulation in xeric environments, we molecularly cloned and analyzed the nuclear receptor subfamily 3 group C member 2 (NR3C2) gene encoding the mineralocorticoid receptor (MR), required for hormone-dependent regulation of genes contributing to body fluid homeostasis. Most vertebrates harbor a single MR homolog. In contrast, we discovered that MR is duplicated in naked mole-rats. The amino acid sequence of naked mole-rat MR1 is 90% identical to its mouse ortholog, and MR1 is abundantly expressed in the kidney and the nervous system. MR2 encodes a truncated protein lacking DNA- and ligand-binding domains of MR1 and is expressed in diverse tissues. Although MR2 did not directly transactivate gene expression, it increased corticosteroid-dependent transcriptional activity of MR1. Our results suggest that MR2 might function as a novel regulator of MR1 activity to fine-tune MR signaling in naked mole-rats.

Supplementary Materials

    • Supplementary Table 1. Primer sequences and BLAST query sequences.
    • Supplementary Table 2. Gene transcriptional activities of aldosterone and cortisol mediated by NMR MR1 with or without MR2.
    • Supplementary Figure 1. Comparison of the kidneys of NMRs and mice.
    • Supplementary Figure 2. Multiple sequence alignment of NMR MRs with the MRs of other species.
    • Supplementary Figure 3. RNA-Seq analysis of NMR MR expression.
    • Supplementary Figure 4. Transcriptional activation of NMR MRs and human MR.
    • Supplementary Figure 5. Coexpression of NMR MR1 and MR2 does not influence their mRNA or protein levels.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© Society for Endocrinology 2021
Page(s):
13
Article Type:
Research Article
Received Date:
16 Mar 2021
Accepted Date:
14 Apr 2021
Print Publication Date:
01 Apr 2021
Online Publication Date:
11 May 2021
Keywords:
mineralocorticoid receptor; naked mole-rat; gene duplication; gene regulation

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