Bis1^A/J
QTL Variant Detail

Summary

• QTL variant: Bis1^A/J
• Name: beta-carboline-induced seizures 1; A/J
• MGI ID: MGI:2159253
• QTL: Bis1 Location: Chr4:136864433-136864536 bp Genetic Position: Chr4, cM position of peak correlated region/allele: 69.44 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

This allele confers sensitivity to beta-CCM (methyl beta-carboline-3-carboxylate) induced myoclonic seizures compared to C57BL/6J. Beta-CCM causes convulsions at high doses, excites anxiety at moderate doses, and enhances learning ability at low doses (J:28058).

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

J:28058

The authors analyzed six mouse strains for susceptibility to (beta)-carboline induced seizures, of which only two gave significant results. In one strain, Je/LeGnc, theauthors detected an association between Bis1 and je. Analysis of (C3XtEso/Gnc x Je/LeGnc)F1 backcross and intercross progeny confirmed the mapping of Bis1 to within ~3.1 cM of je on mouse Chromsome 4.

J:54925

The authors examined the gentic basis of differences in seizure behaviour using a GABAa receptor agoinst beta CCM (methyl beta-carboline-3 carboxylate). A/J mice are more susceptible to beta-CCM induced myoclonic seizures than C57BL/6J mice in both latency to seizure and proportion of tested mice that seized. The previously identified Bis1 QTL was confirmed in a subsequent backcross population (n = 223), D4Mit68 on distal Chromosome 4 is associated with seizure susceptibility (chi square = 10.3; p<0.0012; n = 217) and seizure latency. A LOD score = 2.88 was assigned to this locus and it accounted for 6-9% of the phenotypic variance for this seizure trait. The best-fitting logistic regression model suggests that the C57BL/6J allele at the D4Mit68 locus increased the likelihood of resistance to seizures at 23 fold. Candidate genes in this region include Htr1da, Htr1db and Slc9a1.

References

• Original: J:54925 Gershenfeld HK, et al., Mapping quantitative trait loci for seizure response to a GABAA receptor inverse agonist in mice. J Neurosci. 1999 May 15;19(10):3731-8
• All: 2 reference(s)