Sicd1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Sicd1^C57BL/6J
• Name: seizure-induced cell death 1; C57BL/6J
• MGI ID: MGI:3706137
• QTL: Sicd1 Location: Chr18:80175264-89590914 bp Genetic Position: Chr18, cM position of peak correlated region/allele: 53.28 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers resistance to hippocampal cell death caused by kainic acid-induced seizures compared to FVB/NJ. (J:119634)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Candidate Genes

J:150102

Candidate loci within the Sicd1 QTL region were identified from the 79 Mb to 84 Mb. Galr1 was indicated as a promising candidate, but more analysis needed to be done.

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

J:119634

Linkage analysis was performed on 331 animals from a (FVB/NJ x C57BL/6J)F1 x FVB/NJ backcross population to identify genetic loci involved in kainic acid-induced hippocampal cell death. Parental strain FVB/NJ exhibits extensive hippocampal cell death caused by kainic acid-induced seizures whereas cell death is absent in parental strain C57BL/6J. Backcross animals were administered kainic acid and phenotyped at 8-10 weeks of age. Eighty-seven polymorphic markers at an average resolution of 16 cM were usedfor the genome scan. Three significant QTL were identified accounting for 25% of the trait variance.

Significant linkage to seizure-induced cell death 1 mapped to 57 cM on mouse Chromosome 18 near D18Mit4 (LOD=4.9). This locus explains 8% of the phenotypic variance and is named Sicd1 (seizure-induced cell death 1). This 11 cM interval spans markers D18Mit186 (45 cM) and D18Mit4 (57 cM). Homozygosity for FVB/NJ-derived alleles Sicd1 confers increased hippocampal cell death after kainic acid-induced seizure. Potential candidate genes for Sicd1 include Galr1 (55 cM), Atp9b, and Nfatc1 (54cM). The QTL was confirmed by congenic line analysis. Animals carrying DNA from resistant strain C57BL/6J between D18Mit186 to D18Mit4 on a FVB/NJ susceptible background displayed significantly reduced seizure-induce hippocampal cell death. Previously identified seizure QTL Szs4 maps to 50 cM but is thought to be distinct and separate from Sicd1.

Scid2 (seizure-induced cell death 2) linkage mapped to 29.5 cM on mouse Chromosome 15 (LOD=3.03) between markers D15Mit174 and D15Mit156. This locus explains 4% of the variance. FVB/NJ-derived alleles at D15Mit156 confer susceptibility to hippocampal cell death after kainic acid-induced seizure. This locus also interacts with loci at D10Mit14 (65 cM, LOD=7.56) and D15Mit29 (42.8 cM, LOD=6.13). Candidate genes within the 30 cM 95% confidence include C6 (3 cM), C7 (3 cM), and Sema5a (19.7 cM).

Scid3 (seizure-induced cell death 3) linkage mapped to 3.3 cM on mouse Chromosome 4 (LOD=2.6) between markers D4Mit264 and D4Mit91. C57BL/6J-derived alleles at D4Mit264 confer susceptibility to hippocampal cell death after kainic acid-induced seizures. This locus explains 4% of the variance.

A locus at 33.9 cM (D11Mit177) on chromosome 11also exhibited suggestive linkage (LOD=2.15). Homozygosity for FVB/NJ-derived alleles at D11Mit177 confer susceptibility to seizure-induced hippocampal cell death.

References

• Original: J:119634 Schauwecker PE, et al., Genetic control of sensitivity to hippocampal cell death induced by kainic acid: a quantitative trait loci analysis. J Comp Neurol. 2004 Sep 6;477(1):96-107
• All: 3 reference(s)