Slms1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Slms1^DBA/2J
• Name: sensitivity to locomotor stimulants 1; DBA/2J
• MGI ID: MGI:3688609
• QTL: Slms1 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased sensitivity to ethanol-induced locomotor activity compared to C57BL/6J. (J:114156)
• Inheritance: Other (see notes)

Notes

Slms1 exhibits additive inheritance.

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

J:114156

Linkage analysis was performed on 439 animals from a (C57BL/6J x DBA/2J)F2 intercross to identify QTLs associated with locomotor response to ethanol. Initially, the top and bottom 27.2% phenotypically extreme F2 animals were typed for 186 polymorphic markers. Linkage to locomotor response to 17 mg/kg allopregnanolone was separately analyzed using 403 animals from a (C57BL/6J x DBA/2J)F2 intercross. The top and bottom 22.4% phenotypically extreme F2 animals were typed for 172 polymorphic markers. Parental strain DBA/2J exhibits greater sensitivity to ethanol and allopregnanolone compared to parental strain C57BL/6J.

Significant linkage to ethanol-induced locomotor activity mapped to 62.9 Mb (32 cM) on mouse Chromosome 1. Analysis of a female subset of F2 animals detected suggestive linkage at 79.6 Mb (49.7 cM). This locus is designated Slms1 (sensitivity to locomotor stimulants 1). DBA/2J-derived alleles at Slms1 confer increased response to ethanol.

In a previous study (Palmer et al, 2002), linkage to allopregnanolone-induced locomotor activity mapped to 88.4 cM on mouse Chromosome 2 near Odc-rs2 using BXD RI strains. Reanalysis of this dataset gave similar results with suggestive linkage to ethanol-induced locomotor activity at 118 Mb (65 cM; LOD=1.9) and allopregnanolone-induced locomotor activity at 149 Mb (83 cM; LOD=2.37). Analysis of (C57BL/6J x DBA/2J)F2 animals detected linkage to ethanol-induced locomotor activity at 107.8 Mb (51.5 cM). This locus was also detected in the F2 female subset. Acongenic line carrying C57BL/6J-derived DNA between 20 Mb to 153 Mb on a DBA/2J genetic background exhibited decreased ethanol- and allopregnanolone-induced locomotor activity compared to the DBA/2J parental while a congenic line carrying DBA/2J-derived DNA on a C57BL/6J genetic background exhibited increased ethanol- and allopregnanolone-induced locomotor activity compared to the C57BL/6J parental. Authors hypothesize a QTL on chromosome 2 has pleiotropic effects on sensitivity to locomotor stimulants ethanol and allopregnanolone. This locus is designated Slms2 (sensitivity to locomotor stimulants 2). Previously identified ethanol sensitivity QTLs Ethohila (52 cM), Etlm2 (70 cM), and Actre2 (48 cM) map near Slms2.

Suggestive linkage to ethanol-induced locomotor activity mapped to 124.2 Mb (68 cM) on mouse Chromosome 5 and 112 Mb (61 cM) on mouse Chromosome 9. In the female subset of F2 animals, suggestive linkage to ethanol-induced locomotor activity mapped to 124.2 Mb on mouse Chromosome 5, 85.3 Mb (44 cM) on mouse Chromosome 7, 93.8 Mb (52 cM) on mouse Chromosome 10, and 81.2 Mb (53 cM) on mouse Chromosome 18.

Suggestive linkage to allopregnanolone-induced locomotor activity mapped to 32 Mb (16 cM) on mouse Chromosome 3, 48.3 Mb (26 cM) on mouse Chromosome 5, and 10.5 Mb (2 cM) on mouse Chromosome 12. DBA/2J-derived alleles confer greater sensitivity to allopregnanolone at the loci on chromosomes 3 and 12 whereas C57BL/6J-derived alleles confer greater sensitivity at the chromosome 5 locus.Analysis of a female subset of F2 animals identified suggestive linkage at 126.6 Mb on mouse Chromosome 2, 32 Mb on mouse Chromosome 3, 139.3 Mb on mouse Chromosome 7, and 93.8 Mb on mouse Chromosome 10. Analysis of a male subset of F2 animals identifiedsuggestivelinkage at 82.8 Mb on mouse Chromosome 4, 45.6 Mb on mouse Chromosome 7, and 10.5 Mb on mouse Chromosome 12.

References

• Original: J:114156 Palmer AA, et al., Sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone: A quantitative trait locus study of common genetic influence. Genes Brain Behav. 2006 Oct;5(7):506-17
• All: 1 reference(s)