A specialized cold sensing system in the naked mole-rat

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.