Exq1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Exq1^C57BL/6J
• Name: exploratory and excitability QTL 1; C57BL/6J
• MGI ID: MGI:2157968
• QTL: Exq1 Location: Chr10:119847852-119847939 bp Genetic Position: Chr10, cM position of peak correlated region/allele: 67.89 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers seizure resistance and increased exploratory behavior compared to A/J. (J:54925)
• Inheritance: Not Specified

Notes

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

J:41249

In a genome wide scan using 514 F2 mice derived from crossing (A/J x C57BL/6J)F1s a quantitative trait locus (QTL) for exploratory and excitability behavoir, Eqx1 was significantly associated with markers on mouse Chromosome 10. Exq1 was associated with marker D10Mit237 on distal mouse Chromosome 10 with a reported LOD score of 14.69. Other open field behavioral QTLs loci were mapped to various mouse chromosomes, yet in a personal communication, Dr Gershenfeld suggested Exq1 as being the most notable.

J:44650

Parental strains (A/J x C57BL/6J) and their F1 and 518 F2 intercross offspring were assessed for their fear-like behaviors in light-to-dark (LD) transition paradigm behavior tests. Parental strain C57BL/6J exhibits increased light-dark transitions and increased center time in an open field compared to parental strain A/J. Whole genome scan using 114 polymorphic markers indicated the presence of of a linked quantitative trait locus (QTL) on mouse Chromosome 10 near D10Mit237 (LOD = 9.3). Exq1 is associated with LD transitions during the first and third trials (LD1 and LD3). The Exq1 locus was previously shown by these authors to influence both initial and habituated ambulatory and vertical activity (see J:41249).

A suggestive locus mapped to 49 cM on mouse Chromosome X with LOD = 2.84 at DXMit172. This locus is associated with LD transitions during the third LD transition trial (LD3) but not the first or second.

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. A genome wide screen in an F2 population of these parental strains identified a locus on distal Chromosome 10, near D10Mit180, that displayed an association with seizure susceptibility (chi square =15.77; p = 0.004; n = 271) and seizure latency. A LOD score = 4.29 was assigned to this locus and it accounted for ~25% of the genetic variance and 5.7% of the phenotypic variance for this seizure trait. The best-fitting logistic regression model suggeststhat the A/J allele at the D10Mit180 locus increases the likelihood of seizures at ~2.7 fold. The Chromosome 10 QTL was confirmed in a subsequent backcross population (n = 223). D10Mit237 which is located ~4 cM distal to D10Mit180 displayed significant association to seizure susceptibility (chi square = 19.30; p = <0.0001; n = 214) and seizure latency. A LOD score = 4.36 was assigned to this locus an 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 D10Mit237 locus increased the likelihood of resistance to seizures ~2.8 fold. This Chromosome 10 locus has been named Exq1 because it appears to affect both O-F exploratory behaviour and seizure susceptibility. No known candidate genes are in the telomeric 15 cM region of mouse Chromosome 10.

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: 3 reference(s)