Ctpr1^BALB/cJ
QTL Variant Detail

Summary

• QTL variant: Ctpr1^BALB/cJ
• Name: citalopram responsiveness 1; BALB/cJ
• MGI ID: MGI:3695473
• QTL: Ctpr1 Location: unknown Genetic Position: Chr19, cM position of peak correlated region/allele: 56.28 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: BALB/cJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased responsiveness to citalopram compared to A/J. (J:108843)

Notes

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

J:108843

Linkage analysis was performed on animals from a (BALB/cJ x A/J)F2 intercross to identify QTLs associated with response to the antidepressant citalopram. Parental strain BALB/cJ is a high-responder whereas A/J is a low-responder. Animals were assessed bytail suspension test (STS) following injection with 20 mg/kg of citalopram solution. One hundred six microsatellite markers at an average spacing of 20 cM were used for the genome scan. Forty-six highest-responding F2 animals and 46 lowest-responding F2 animals were genotyped.

The locus with highest significance mapped to 54 cM on mouse Chromosome 19 near D19Mit71 (P=0.00101. This locus explains approximately 14% of the variance and is designated Ctpr1 (citalopram responsiveness 1). The Ctpr1 QTL interval spans 50 cM to 55 cM. BALB/cJ-derived alleles at Ctpr1 appear to confer increased responsiveness to citalopram. Potential candidate genes in this region include Adra2a (50 cM), Adrb1 (51 cM), and Slc18a2 (53 cM). Sequence analysis of BALB/cJ and A/J candidate genes revealed 4 single nucleotide polymorphisms in Slc18a2, two of which result in amino acid changes in highly conserved regions of the protein.

Suggestive linkage to citalopram responsiveness mapped to 72 cM on mouse Chromosome 7 near D7Mit259 (P=0.003) and 45 cM on mouse Chromosome 12 near D12Mit118 (P=0.003). A/J-derived alleles at D7Mit259 appear to confer increased citalopram responsiveness. At D12Mit118, the most responsive F2 animals tended toward A/J or BALB/cJ homozygosity.

References

• Original: J:108843 Crowley JJ, et al., Pharmacogenomic evaluation of the anti-depressant citalopram in the mouse tail suspension test. Neuropsychopharmacology. 2006 Nov;31(11):2433-42
• All: 1 reference(s)