Marq2^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Marq2^DBA/2J
• Name: methamphetamine response QTL 2; DBA/2J
• MGI ID: MGI:3590524
• QTL: Marq2 Location: unknown Genetic Position: Chr9, cM position of peak correlated region/allele: 71.49 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased methamphetamine-induced activation of locomotor activity compared to C57BL/6J. (J:100797)

Notes

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

J:100797

A combined analysis using behavioral QTL (bQTL) mapping and expression QTL (eQTL) mapping was employed to identify loci associated with methamphetamine-activated locomotor activity in animals from short term selection lines. A high methamphetamine responding line (HMACT) and a low methamphetamine (LMACT) responding line were bred from C57BL/6J and DBA/2J progenitors for 4 generations. The HMACT line exhibits 5.3-fold greater locomotor activity after methamphetamine administration compared to the LMACT line. 80 microsatellite markers were used to map bQTL using a DNA pooling strategy with 82 HMACT animals and 62 LMACT animals. Microarray analysis was used to identify eQTL. Methamphetamine response QTL were detected on mouse Chromosomes 5, 9, 11, 12, and 15.

Marq1 (methamphetamine response QTL 1) mapped to 53 cM on mouse Chromosome 5 with LOD=5.5 near D5Mit95. DBA/2J-derived alleles are highly enriched at D5Mit95 in the HMACT line.

Marq2 (methamphetamine response QTL 2) mapped to 71 cM on mouse Chromosome 9 with LOD=4.8 near D9Mit18. DBA/2J-derived alleles are highly enriched at D9Mit18 in the HMACT line.

Marq3 (methamphetamine response QTL 3) mapped to 65 cM on mouse Chromosome 11 with LOD=3.5 near D11Mit338. DBA/2J-derived alleles show enrichment at D11Mit338 in the LMACT line. Ppp1r1b (Darpp-32) is a potential candidate gene mapping to approximately 98 cM. HMACT animals express 35% more Ppp1r1b mRNA compared to LMACT animals. Other potential candidate genes for Marq3 are Pparbp (61 cM) and Gria1 (31 cM).Pparbp and Gria1 mRNA expression are both significantly higher in LMACT animals compared to HMACT animals.

Marq4 (methamphetamine response QTL 4) mapped to 47 cM on mouse Chromosome 12 with LOD=4.5 near D12Mit157. DBA/2J-derived alleles are highly enriched at D12Mit157 in the HMACT line.

Marq5 (methamphetamine response QTL 5) mapped to 29 cM on mouse Chromosome 15 with LOD=4.5 near D15Mit72. DBA/2J-derived alleles show enrichment at D15Mit72 in the HMACT line. Csnk1e is a potential candidate gene mapping to the Marq5 peak. Csnk1e exhibits significantly increased expression in HMACT animals compared to LMACT animals.

References

• Original: J:100797 Palmer AA, et al., Gene expression differences in mice divergently selected for methamphetamine sensitivity. Mamm Genome. 2005 May;16(5):291-305
• All: 1 reference(s)