Abstracts

Patients with autosomal dominant lateral temporal epilepsy (ADLTE) with auditory features were recently found to harbor mutations in the non-ion channel protein LGI1. To determine if mutations of this protein are sufficient to produce epilepsy, we created a transgenic mouse from the full-length LGI1 gene engineered to contain an epilepsy-associated gene mutation. As a control, other transgenic mice were also created that carry extra copies of the wild-type, full-length LGI1 gene. We predicted that ADLTE mutant LGI1 will produce epilepsy in mice., Mice of each genotype were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes for polysomnogram recording. After [gt] 9 days of recovery from surgery, they were transferred to recording cages in a sound-attenuated chamber with a 12 hr light/dark (LD) cycle (30 lux; lights on at 7:00 A.M. and off at 7:00 P.M.) and a constant temperature (22-24[deg]C) for 5 days of continuous recording. Video recordings were also performed during the last day in a subset of mice. The signals were digitally filtered (EEG, 0.3-30 Hz; EMG, 2-100 Hz) and semi-automatically scored in 10 sec epochs as wake, NREM sleep, REM sleep, or seizures. Sleep analyses were focused on the last recording day. The preliminary scoring was visually inspected and corrected when appropriate., Mutant LGI1 transgenic (n=5), full-length LGI1 transgenic (n=4), and wild-type littermate (n=5) mice showed no significant differences in the hourly amounts of NREM, REM, or wakefulness. Seizures induced by pentylene-tetrazol (60 mg/kg, i.p.) were also examined., ADLTE mutant LGI1 transgene does not significantly influence the pattern of sleep. We are currently testing the hypothesis that mutant LGI1 is sufficient to cause epilepsy., (Supported by: Funded by National Institute of Neurologic Disease (MPA), Burrough Wellcome Fund Career Award (MPA), and Beth Israel Deaconess Medical Center.)