CONGENIC STRAINS REVEAL EFFECTS OF THE EPILEPSY QUANTITATIVE TRAIT LOCUS, EL2, SEPARATE FROM OTHER EL LOCI

Congenic mouse strains made by transferring epilepsy predisposing alle les El1, El2, and El3 from the EL/Suz strain to the ABP/Le recipient w ere tested for seizure frequency following gentle rhythmic stimulation . Mice homozygous for El2, but not El1 or El3, experienced seizures mu ch more frequently than ABP controls, while respective El1 homozygotes and El2 heterozygotes had only a modest increase over ABP, and El3 ho mozygotes showed no increase. Association between marker genotypes and seizure frequency in small intra-strain crosses showed that the pheno typic effects of El2 map to the selected interval, and that segregatio n of El2 accounts for virtually all genetic effects. However, in separ ating El2 from other EL susceptibility alleles, the seizure frequency phenotype was weaker and less heritable than in crosses between parent al strains. These results confirm El2 as an important QTL and show tha t it has significant phenotypic effects in the absence of other EL-der ived alleles, including Ell. In addition, the present localization of El2 on Chr 2 suggests several potential candidate genes for El2, inclu ding the beta subunit of phospholipase-C. The approach to dissecting c omplex traits by making congenic strains for individual QTL is discuss ed.