Hpic4^LP/J
QTL Variant Detail

Summary

• QTL variant: Hpic4^LP/J
• Name: haloperidol induced catalepsy 4; LP/J
• MGI ID: MGI:2389368
• QTL: Hpic4 Location: unknown Genetic Position: Chr14, Syntenic

Variant origin

• Strain of Specimen: LP/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased responsiveness to haloperidol induced catalepsy compared to BALB/cJ. (J:58047)
• Inheritance: Not Specified

Notes

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

J:68417

The authors use a novel approach in mapping QTLs involved in murine behavioral phenotypes. A genome wide scan was performed with (C57BL/6J x DBA/2J)F2 and (BALB/cJ x LP/J)F2 intercrosses crosses to map QTLs affecting in three different behavioral phenotypes. The strains chosen have widely differing polymorphisms and phenotypes and the QTLs identified from each cross do not appear to have overlap. Two significant QTLs (LOD>4.3 threshold), Hpic3 and Hpic4, for haloperidol-induced catalepsy mapped to 0 - 20 cM and 35 - 60 cM on mouse Chromosome 14, respectively. Both QTLs, Hpic3 and Hpic4, were identified from the (BALB/cJ x LP/J)F2 intercross. The authors also used a subtractive method to resolve a broad QTL (60-100 cM) for basal activity on distal Chromosome 1. Genotyping information from (C57BL/6J x DBA/2J)F2, (C57BL/6J x A/J)F2, and (C57BL/6J x BALB/cJ)F2 intercrosses was used to screen 254 microsatellite markers across the locus. Only markers polymorphic between all four strains (35 markers) were further analyzed. These highly informative markers revealed 2 separate QTLs: one previously reported by Talbot for basal activity at 67 cM and another at 95 - 105 cM.

J:58047

Linkage analysis was performed on 1037 animals from a (BALB/cJ x LP/J)F2 intercross to identify loci associated with sensitivity to haloperidol-induced catalepsy. Parental strain BALB/cJ exhibits 30-fold more sensitivity to haloperidol-induced catalepsy (responsive) compared to parental strain LP/J (non-respsonsive). Genome scan was conducted with polymorphic microsatellite markers spaced on average 20 cM apart. Genomic regions reaching LOD>3 were fine mapped with additional markers.

Significant linkageto haloperidol-induced catalepsy mapped to mouse Chromosome 14 near D14Mit121 (16.8 cM; LOD=6.9) and D14Mit196 (47 cM; LOD=6.4). These loci are named Hpic3 (haloperidol induced catalepsy 3) and Hpic4 (haloperidol induced catalepsy 4), respectively. LP/J-derived alleles confer non-reponsiveness to haloperidol induced catalepsy at Hpic3 and Hpic4. Hpic3 accounts for 9.6% of the phenotypic variance and Hpic4 accounts for 9% of the phenotypic variance. Potential candidate genes mapping near Hpic3 include Chat(10 cM), Grid1 (13.5 cM), Glud1 (15.5 cM), hph1 (19.5 cM), and Chrna2 (formerly Acra2; 20 cM). The piebald locus Ednrb (51 cM) shows linkage to haloperidol sensitivity and maps near the seratonin receptor Htr2a (41.5 cM). However, Htr2a receptor binding activity does not differ significantly between BALB/cJ and LP/J.

References

• Original: J:68417 Hitzemann R, et al., Effect of genetic cross on the detection of quantitative trait loci and a novel approach to mapping QTLs. Pharmacol Biochem Behav. 2000 Dec;67(4):767-72
• All: 2 reference(s)