J:30433

(ABP/LeJ x EL/Suz)F2 and (EL/Suz x DDY/Jcl)F2 intercross populations and a (EL/Suz x DDY/Jcl)F1 x DDY/Jcl backcross population were used to map QTLs associated with seizure susceptibility. Parental strain EL/Suz is susceptible to spontaneous epileptic seizures whereas parental strains ABP/LeJ and DDY/Jcl are resistant. Seizure susceptibility appears to follow partial dominant inheritance since F1 hybrids exhibit seizure frequencies similar to EL/Suz parentals. Seizure susceptibility loci El3, El4, El5, and El6 were mapped.

El3 mapped to mouse Chromosome 10 in the (ABP/LeJ x EL/Suz)F2 intercross with a maximum LOD score of 3.8 at 44 cM in linkage to D10Mit42 (P<0.0001). EL/Suz-derived alleles confer dominant seizure susceptibility at El3.

El4 mapped to mouse Chromosome 9 in the (ABP/LeJ x EL/Suz)F2 intercross with a maximum LOD score of 3.4 at 29 cM in linkage to D9Mit4 (P<0.009) and Bmp5 (P<0.005).

7.13.2015 Curator Note: Because two different crosses were used here to map El4 we consider each to be a separate mapping study. We have assigned offical nomenclature to the suggestive QTL identified in the (EL/Suz x DDY/Jcl)F1 x DDY/Jcl backcross, labeling it El8, since it is interative with El5 in the (EL/Suz x DDY/Jcl)F2 intercross.

El8 showed suggestive linkage at D9Mit10 (P<0.007) in the (EL/Suz x DDY/Jcl)F1 x DDY/Jcl backcross with a LOD score of 2. EL/Suz-derived alleles confer seizure susceptibility in an additive or recessive fashion at El8. Epistatic interaction involving El8 and El5 was detected in the (EL/Suz x DDY/Jcl)F2 intercross.

El5 mapped to mouse Chromosome 14 in the(EL/Suz x DDY/Jcl)F2 intercross with a maximum LOD score of 6.7 at 54.7 cM in linkage to D14Mit123. EL/Suz-derived alleles confer seizure susceptibility in an additive or dominant fashion at El5. Possible candidate genes inthe region of El5 are the neurofilament gene, Nfl, and seratonin receptor, Htr2a.

El6 mapped to mouse Chromosome 11 in the (EL/Suz x DDY/Jcl)F2 intercross and the (EL/Suz x DDY/Jcl)F1 x DDY/Jcl backcross with a maximum LOD score of 3.9 at 68 cM in linkage to D11Mit100. DDY/Jcl-derivedalleles confer seizure susceptibility in a recessive or additive fashion at El6.

J:114157

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.