GeneSet Information

Tier II GS135417 • beta-carboline induced seizures 4 (Bis4, Published QTL Chr 7)

DESCRIPTION:

QTL associated with beta-carboline induced seizures 4. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (34527929)

LABEL:

QTL-Bis4-Mouse-Chr 7

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Gershenfeld HK, Neumann PE, Li X, St Jean PL, Paul SM

TITLE:

Mapping quantitative trait loci for seizure response to a GABAA receptor inverse agonist in mice.

JOURNAL:

The Journal of neuroscience : the official journal of the Society for Neuroscience May 1999, Vol 19, pp. 3731-8

ABSTRACT:

To define the genetic contributions affecting individual differences in seizure threshold, a beta carboline [methyl-beta-carboline-3-carboxylate (beta-CCM)]-induced model of generalized seizures was genetically dissected in mice. beta-CCM is a GABAA receptor inverse agonist and convulsant. By measuring the latency to generalized seizures after beta-CCM administration to A/J and C57BL6/J mice and their progeny, we estimated a heritability of 0.28 +/- 0.10. A genome wide screen in an F2 population of these parental strains (n = 273) mapped quantitative trait loci (QTLs) on proximal chromosome 7 [logarithm of the likelihood for linkage (LOD) = 3.71] and distal chromosome 10 (LOD = 4.29) for seizure susceptibility, explaining approximately 22 and 25%, respectively, of the genetic variance for this seizure trait. The best fitting logistic regression model suggests that the A/J allele at each locus increases the likelihood of seizures approximately threefold. In a subsequent backcross population (n = 223), we mapped QTLs on distal chromosome 4 (LOD = 2.88) and confirmed the distal chromosome 10 QTLs (LOD = 4.36). In the backcross, the C57BL/6J allele of the chromosome 10 QTL decreases the risk of seizures approximately twofold. These QTLs may ultimately lead to the identification of genes influencing individual differences in seizure threshold in mice and the discovery of novel anticonvulsant agents. The colocalization on distal chromosome 10 of a beta-CCM susceptibility QTL and a QTL for open field ambulation and vertical movement suggests the existence of a single, pleiotropic locus, which we have named Exq1. PUBMED: 10234005
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Annotation Information



Chromosomes, Human, Pair 7 (D002897)
Chromosomes, Human, Pair 4 (D002894)
Seizures (D012640)
Alleles (D000483)
Individuality (D007206)
Walking (D016138)
Chromosomes (D002875)
Chromosomes, Human, Pair 10 (D002879)
Quantitative Trait Loci (D040641)
Movement (D009068)
Logistic Models (D016015)
Organization and Administration (D009934)
Regression (Psychology) (D012043)
Identification (Psychology) (D007062)
abnormal seizure response to inducing agent (MP:0009357)
chromosome (GO:0005694)

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