Abstracts

Febrile seizures (FS) are the most common form of convulsion, occurring in 2-5% of infants in Europe and North America and 6-9% of infants in Japan. Mouse models for febrile seizures will provide a system in which to study the molecular events involved. In humans, febrile seizures occur in infants (6 months to 5 years) and are associated with a rise in body temperature. We simulate febrile seizures in infant mice by subjecting them to whole body hyperthermia. A method originally used to induce febrile seizures in rats (Baram et al. Dev. Brain Res. 1997; 98:265-270) is currently being used to determine the threshold of febrile seizures in mice. Mice that are 14 days old are subjected to hyperthermia by gradually raising the air temperature. After approximately 5 minutes the mice exhibit motor seizures. The time to seizure onset and core body temperature at the time of onset are recorded. Detailed protocols are available at: http://www.tnmouse.org/neuromutagenesis/epilepsy.html To date we have tested over 30 ENU mutagenized pedigrees. Several pedigrees showed significant deviation from the controls for either the temperature at which the seizure occurred or the time taken to onset of the seizure. These pedigrees are currently being retested prior to mapping and identification of the underlying mutation. Mortality is normally low for the hyperthermia procedure ([lt]5%), however certain pedigrees (eg DBA2J) show high mortality rates. Pedigrees with high mortality also had delayed seizure onset with a higher core body temperature at onset. The increased mortality may be due to the higher core temperature reached during the extended time in the hyperthermia chamber. An extended strain survey is currently underway. We have developed a reliable and rapid screen for febrile seizures which is ideal for testing ENU mutagenized mice. We have also demonstrated strain differences in inbred mice, suggesting that genetic background plays a role in susceptibility to febrile seizures. (Supported by the Epilepsy Foundation (Wallace) and National Institutes of Health U01MH06197 (Goldowitz))