GABAA receptor α1 subunit knockout mice: a novel model of essential tremor

摘要: Deletion of GABA A receptor al subunits in mice results in a phenotype of kinetic tremor that mimics certain features of essential tremor disease. Knockout mice exhibit a tremor of approximately 16 to 22 Hz, whereas wild-type and heterozygous mice exhibit a physiological tremor in the range of 25 to 40 Hz. The tremor is observed early in life, and the power or amplitude of the oscillation is increased in 8-month-old mice compared to 4-month-old mice. The GABAA benzodiazepine receptor agonist diazepam and the GABAergic neuroactive steroid allopregnanolone exacerbate the tremor, whereas ethanol completely inhibits the tremor. Since the etiology of essential tremor is unknown, this animal model of genetic essential tremor may lead to an understanding of the pathophysiology of the disease and provide a valuable model system to develop therapeutic interventions.