Development of a New Genetic Model for Absence Epilepsy: Spike-Wave Seizures in C3H/He and Backcross Mice

To characterize the genetic basis of spike-wave discharges (SWDs) detected by electroencephalography (EEG) in C3H/He mice, substrains of C3H mice were evaluated by EEG and sensitivity to ethosuximide. Crosses with the SWD-negative strain C57BL/6J were performed to map the underlying gene(s). C3H/He substrains exhibited a modest incidence (average of 19 SWDs per hour) of 7-8 Hz SWDs when at rest, compared with the C3HeB/Fe subline (four SWDs per hour). In the mapping backcross, however, many mice showed a very high incidence (50-220 SWDs per hour) throughout the recording period. SWDs were first detected at 3.5 weeks of age, were associated with behavioral arrest, were suppressed by ethosuximide, and were strongest in the cerebral cortex and thalamus. The major C3H determinant of SWDs, spkw1 (spike-wave 1), mapped to chromosome (Chr 9), and together with a C57BL/6J determinant on Chr 8, spkw2, accounted for more than one-half of the phenotypic variation in the backcross mice. The modest SWD incidence in C3H/He mice and the high incidence in backcrosses implies that SWD could be a confounding variable for other behaviors. Because C3H/He mice have no other brain abnormalities, they are an attractive alternative for studying idiopathic absence epilepsy.