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bioRxiv · 10.1101/2025.09.25.678629

A specialized cold sensing system in the naked mole-rat

Wang, L.·Gomez-Restrepo, A.·Niqula, A.·Jouhanneau, J.-S.·Mendez-Aranda, D.·Luo, W.·Poulet, J. F. A.·de la Pena, E.·Viana, F.·Begay, V.·Lewin, G. R.

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Abstract

Avoiding cold or seeking warmth are universal animal needs. Homeothermic mammals maintain a constant body temperature despite fluctuating ambient temperatures. One exception is the naked mole-rat which lacks effective thermogenesis. We show that the naked mole-rat has evolved a greatly expanded cold sensing system. Compared to mice, this species has many more cold-sensitive sensory neurons and most express the cold-activated TRPM8 channel. The naked mole-rat TrpM8 gene harbors a unique upstream exon that when translated produces a TRPM8 protein with a 71 amino acid N-terminal extension. When expressed, the N-terminal extension prevents membrane targeting and abolishes TRPM8 function. Splice forms lacking the extension formed functional cold and menthol activated channels in vivo. Additionally, many naked mole-rat sensory neurons use a TRPM8-independent mechanism to detect cold. Thus, we identified molecular changes that confer both sensitivity and flexibility to cold sensing in a species that is critically dependent on following thermal cues.

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Wang, L., Gomez-Restrepo, A., Niqula, A., Jouhanneau, J.-S., Mendez-Aranda, D., Luo, W., Poulet, J. F. A., de la Pena, E., Viana, F., Begay, V., Lewin, G. R.. 2025-09-25. A specialized cold sensing system in the naked mole-rat. https://doi.org/10.1101/2025.09.25.678629

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