ENVIRONMENTAL-INFLUENCES ON EPILEPSY GENE-MAPPING IN EL MICE

The epileptic EL mouse has been studied extensively as a genetic model for idiopathic complex partial seizures in humans. The seizures in EL mice occur during routine handling at approximately 90 days of age, b ut can be induced at younger ages (50 days) by repeated rhythmic vesti bular stimulation, e.g., tossing. Six seizure frequency quantitative t rait loci (QTLs), ElI-El6, were previously mapped in crosses between E L and non-epileptic strains using mechanical tossing procedures beginn ing at 30 days of age. The presence of these seizure frequency QTLs de pended upon genetic background and the type of cross, Here we confirm Chromosome 2 and 9 QTLs in a backcross to the seizure-resistant ABP/Le J strain with mice tested beginning at 200 days of age. However, the m apping of epilepsy genes was influenced by the seizure testing procedu re, i.e., repeated tossing. The maximum Z-score for Ell (Chromosome 9) was 3.7 after 6 tests, bur decreased to 2.4 after 15 tests. In contra st, the maximum Z-score for El2 (Chromosome 2) was 2.0 after 6 tests, but increased to 3.9 after 15 tests.In addition to nonallelic interact ions (epistasis),our findings indicate that the genetic complexity of tossing-induced seizure susceptibility in EL mice also arises from gen otype-environmental interactions involving the seizure test, seizure h istory, and age.