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Issue 140 Summer 2021

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Mineralocorticoid receptor signalling in the naked mole-rat

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Naked mole-rats (Heterocephalus glaber) are mouse-sized rodents with unique physiological features, including exceptional longevity and resistance to age-related diseases. They inhabit subterranean burrows in the arid savannas of North East Africa and are unable to access free water. Control of fluid homeostasis in the naked mole-rat is poorly understood.

The mineralocorticoid receptor (MR) contributes to fluid homeostasis by modulating sodium balance and blood pressure in response to aldosterone signalling in the kidney. Tetrapods typically carry only one copy of the MR gene, but Bactrian camels carry two copies, putatively due to evolutionary adaptation to an arid, desert environment. Although the whole genome of the naked mole-rat has been sequenced, the genomic sequence of MR is incomplete.

To investigate how fluid homeostasis is controlled in the naked mole-rat, Oka and colleagues molecularly cloned and analysed the naked mole-rat MR gene. They discovered that it is duplicated in naked mole-rats, resulting in two receptors: MR1 and MR2. MR1 is 90% identical to its mouse orthologue and MR2 encodes a truncated protein that lacks the DNA- and ligand-binding domains of MR1. In transcriptional activation assays, MR2 alone did not induce reporter gene expression, but co-expression of MR1 and MR2 augmented MR1-dependent transactivation activity in response to corticosteroids.

These results suggest that MR2 functions as a regulator of MR1 activity in naked mole-rats, which may contribute to evolutionary adaptations to control of fluid homeostasis in arid environments.

Read the full article in Journal of Molecular Endocrinology 66 299–311

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