Experiment
Previously identified loci (chr 2, 9, and 10) associated with idiopathic generalized epilepsy were examined in (ABP/LeJ x EL/Suz)F2 animals to determine their effect in different environments. Parental strain EL/Suz is susceptible to spontaneous epileptic seizures whereas parental strain ABP/LeJ is non-epileptic. Seizure susceptibility appears to follow dominant inheritance after repeated testing in young or old mice, but appears to follow recessive inheritance in a single test in old mice. Animals were tested under 3 different environments. Environment 1 involved young animals (age 30 days) tested for seizures at four 30-day intervals, with the last test used for genotype analysis. Environment 2 involved old animals (age 150 days) tested once for seizures. Environment 3 involved old animals (age 150 days) tested for seizures at four 30-day intervals, with the last test used for genotype analysis.
Linkage to El4 (epilepsy 4) on mouse Chromosome 9 was detected in Environment 1 near D9Mit22 (LOD=4.35). This locus explained 20.1% of the variance and the QTL interval spanned D9Mit22 (28 cM) to D9Mit32 (35 cM). A novel locus named Elnv (epilepsy nave) was identified between D9Mit188 (9 cM) and D9Mit2 (17 cM) in Environment 2 with LOD=3.46. Elnv explained 9.2% of the variance. El4 and Elnv were also detected in Environment 3 (LOD=4.28 and LOD=6.29, respectively). El4 explained 12.7% of the variance, and Elnv explained 15.7% of the variance in Environment 3. Gria4 (8 cM) is a potential candidate gene for Elnv.
Linkage to El2 (epilepsy 2) on mouse Chromosome 2 was detected in Environment 1, but only in females. El2 mapped between D2Mit30 (69 cM) and D2Mit21 (80 cM) with LOD=3.72, and accounted for 35.2% of the variance.
Suggestive linkage to El3 (epilepsy 3)on mouse Chromosome 10 was detected in Environment 2 (LOD=2.29). El3 mapped between D10Mit42 and D10Mit134, and accounted for 5.6% of the variance.
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