Audiogenic seizure susceptibility in thyroid hormone receptor beta-deficient mice.
As early-onset hypothyroidism produces audiogenic seizure susceptibility (AGS) in rodents, the role of TR alpha 1 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 differing from mouse strains where AGS is age-restricted. Thrb(tm1/tm1) mice display AGS whether on a mixed 129/Sv x C57BL/6J or congenic C57BL/6J background. 27% of wild-type mice on the mixed and 0% on the congenic background exhibited AGS. The inability of Thrb(tm1/tm1) mice to downregulate the response to sustained acoustic stimulation may reside in the brain or in the auditory system itself as Thrb(tm1/tm1) mice also display auditory deficits. The AGS phenotype identifies a novel neurological role for TR beta.
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Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Pedraza
P E
PE
Faris
J S
JS
Vennström
B
B
Curran
T
T
Morreale de Escobar
G
G
Forrest
D
D
D017668:Age of Onset; D000818:Animals; D001306:Auditory Pathways / Q000503:physiopathology*; D020195:Epilepsy, Reflex / Q000503:physiopathology*; D007037:Hypothyroidism / Q000503:physiopathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*
D011988:Receptors, Thyroid Hormone