Audiogenic seizure susceptibility in thyroid hormone receptor beta-deficient mice

As early-onset hypothyroidism produces audiogenic seizure susceptibility (A GS) in rodents, the role of TR alpha1 and TR beta thyroid hormone receptors in AGS was investigated. AGS occurs in mice lacking specifically TR beta ( Thrb(tm1/tm1)) and is marked by early onset and persistence, thereby differ ing from mouse strains where AGS is age-restricted. Thrb(tm1/tm1) mice disp lay AGS whether on a mixed 129/Sv x C57BL/6J or congenic C57BL/6J backgroun d. 27% of wild-type mice on the mixed and 0% on the congenic background exh ibited AGS. The inability of Thrb(tm1/tm1) mice to downregulate the respons e to sustained acoustic stimulation may reside in the brain or in the audit ory system itself as Thrb(tm1/tm1) mice also display auditory deficits. The AGS phenotype identifies a novel neurological role for TR beta. NeuroRepor t 12:2359-2362 (C) 2001 Lippincott Williams & Wilkins.