El2^EL
QTL Variant Detail

Summary

• QTL variant: El2^EL
• Name: epilepsy 2; EL
• MGI ID: MGI:2155257
• Synonyms: EL
• QTL: El2 Location: Chr2:122207146-142532135 bp Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: EL

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to epileptic seizures compared to ABP/LeJ. (J:11381)
• Inheritance: Not Specified

Notes

The EL mouse strain was developed from mice with an increased succeptibility for epilepsy. These mice were first reported as a spontaneous mutation arising in the DDY strain. The succeptibility for epilepsy was subsequently shown to be the result of alleles at two or more loci.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:11381

(DBA/2J x EL)F1 x DBA/2J and (ABP/LeJ x EL)F1 x ABP/LeJ backcross populations were used to map QTLs associated with susceptibility to epileptic seizures. Parental strain EL is highly susceptible to epileptic seizures whereas parental strains DBA/2J and ABP/LeJ are resistant. F1 hybrid animals exhibit seizure susceptibility to a lesser degree than parental strain EL.

A locus with significant association to epileptic seizures, El1, was detected on mouse Chromosome 9 (P<0.001) in both backcross populations. El1 maps near Mpmv27, Myo5a, Bmp5, and Glb1 and gives a peak LOD score of 5.88 between Glb1 and Bmp5. A locus significantly linked to seizures, El2, was detected on mouse Chromosome 2 (P<0.001) in the (ABP/LeJ x EL)F1 x ABP/LeJ backcross population. El2 is linked to Mpmv28 with a peak LOD score of 5.2.

7.13.2015 Curator Note: Because two different crosses were used in this study we consider each QTL to be unique. We have left the QTL identified here, using the (DBA/2J x EL)F1 x DBA/2J backcross, with the original El1 nomenclature. We have named the QTL identified using the (ABP/LeJ x EL)F1 x ABP/LeJ backcross as El7.

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.

References

• Original: J:11381 Rise ML, et al., Genes for epilepsy mapped in the mouse. Science. 1991 Aug 9;253(5020):669-73
• All: 9 reference(s)