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A specialized cold sensing system in the naked mole-rat

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Item Type:Preprint
Title:A specialized cold sensing system in the naked mole-rat
Creators: Wang, Lin ORCID logoORCID: https://orcid.org/0000-0002-8395-6184, Gomez-Restrepo, Alejandro, Niqula, Amanda ORCID logoORCID: https://orcid.org/0000-0003-3141-2967, Jouhanneau, Jean-Sebastien ORCID logoORCID: https://orcid.org/0000-0001-8804-5198, Mendez-Aranda, Daniel ORCID logoORCID: https://orcid.org/0000-0001-9668-941X, Luo, Wenhan ORCID logoORCID: https://orcid.org/0000-0001-5202-8855, Poulet, James F.A. ORCID logoORCID: https://orcid.org/0000-0003-0296-5415, de la Pena, Elvira ORCID logoORCID: https://orcid.org/0000-0001-5961-5067, Viana, Felix, Bégay, Valérie ORCID logoORCID: https://orcid.org/0000-0002-9002-4211 and Lewin, Gary R. ORCID logoORCID: https://orcid.org/0000-0002-2890-6352
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 Nterminal 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 molerat 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.
Keywords:Non-Model Organism, Poikilotherm, Sensory Coding, Cold Avoidance, Thermal Transduction, Splicing, Ion Channels, Animals, Mice, Naked Mole-Rats
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2025.09.25.678629
Date:25 September 2025
Official Publication:https://doi.org/10.1101/2025.09.25.678629

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