TMEM16C is involved in thermoregulation and protects rodent pups from febrile seizures
Tongfei Wang, Chao Chen, Fen Huang, Shengjie Feng, Jason Tien, João M. Bráz, Allan I. Basbaum, Yuh Nung Jan, Lily Yeh Jan
Abstract
Significance As the most common convulsive disorder in infancy and childhood, affecting 2 to 5% of American children in their first 5 y of life, febrile seizures (FSs) are associated with genetic risk factors, including the Tmem16c ( Ano3 ) gene. Whereas central neuronal hyperexcitability has been implicated in FSs, whether FSs may result from compromised body temperature regulation is unknown. To approach this question, we developed rodent models of FSs associated with deficient thermoregulation, including conditional knockout mice with TMEM16C eliminated from a hypothalamic neuronal population important for maintaining body temperature but not from most of the cortical and hippocampal neurons and sensory neurons. Our findings raise the possibility that impaired homeostatic thermoregulation could contribute to the risk of FSs.