Alcw9^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Alcw9^DBA/1J
• Name: alcohol withdrawal 9; DBA/1J
• MGI ID: MGI:3580125
• QTL: Alcw9 Location: Chr11:35578616-44065931 bp Genetic Position: Chr11, Syntenic

Variant origin

• Strain of Specimen: DBA/1J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased alcohol withdrawal severity compared to DBA/2J. (J:98588)
• Inheritance: Recessive

Notes

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

J:98588

Haplotype analysis was used to fine map previously identified QTLs Alcw3 (18 cM) and Pbw3 (15 cM) to a 3 cM interval on proximal mouse Chromosome 11. These loci are associated with alcohol and pentobarbital withdrawal severity, and in the current study the refined interval also shows linkage to zolpidem withdrawal. A new QTL symbol will be designated for the zolpidem withdrawal severity phenotype, Zolw1 (zolpidem withdrawal 1). The DBA/1J-derived allele confers increased withdrawal severity for all 3 sedatives in a recessive mode of inheritance.

5.18.2015 Curator Note: Becasue Alcw3 was originally mapped in J:36168 using 21 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred mice in 1996, which differs from the cross used here, we consider the current study aseparate mapping experiment and have named this QTL Alcw9.

Haplotype analysis was performed on (DBA/1J x DBA/2J)F2 mice. The DBA/2J parental strain exhibits severe withdrawal from alcohol and pentobarbital compared to the DBA/1J parental strain. 27 microsatellite markers surrounding the marker of strongest linkage, D11Mit174, were typed for haplotype analysis. The interval between D11Mit231 (17 cM) and D11Mit21 (20) is the most likely location of Alcw9, Pbw3, and Zolw1. This interval contains 34 genes. Genes of the Gaba receptor subunit cluster (Gabrg2, Gabra1, Gabra6, Gabrb2, Gabrp) map to this interval and are considered candidate genes. A previously identified seizure QTL named Szs10 (27 cM) maps near this interval.

Candidate gene Gabrg2 shows segregation with the withdrawal severity phenotype. (DBA/1J x DBA/2J)F2 animals homozygous for DBA/1J-derived alleles at Gabrg2 exhibit increased alcohol, pentobarbital, and zolpidem withdrawal severity compared to animals homozygous for DBA/2J-derived alleles. In addition, Gabrg2 also exhibits sequence and expression variation between DBA/1J and DBA/2J. For these reasons, Gabrg2 is considered a very strong candidate gene.

References

• Original: J:98588 Hood HM, et al., Fine mapping of a sedative-hypnotic drug withdrawal locus on mouse chromosome 11. Genes Brain Behav. 2006 Feb;5(1):1-10
• All: 1 reference(s)