Identification of quantitative trait loci for haloperidol-induced catalepsy on mouse chromosome 14.
Previous studies have established that neuroleptic-induced catalepsy in mice is a highly heritable trait. The current study focuses on the detection of quantitative trait loci (QTL) for haloperidol-induced catalepsy in a BALB/cJ x LP/J F(2) intercross. One thousand thirty-seven F(2) animals were phenotyped and divided into four categories: very responsive (RR), responsive, nonresponsive, and very nonresponsive (NN). The RR and NN phenotypes comprised approximately 18% each of the total and differed in their haloperidol sensitivity by >10-fold. Sex differed significantly between the NN and RR groups (chi(2) = 14.0; p <.0002); females comprised 58% of the RR individuals but only 38% of the NN individuals. The difference between the extreme phenotypes in the number of piebald animals was highly significant (chi(2) = 30, p <. 00001). Eight percent of the RR individuals were piebald compared with 30% of the NN individuals. A genome wide scan confirmed the presence of a QTL (peak LOD = 6.4) on chromosome 14 near the piebald (Ednrb) and 5-hydroxytryptamine(2A) (Htr2a) loci. Although the parental BALB/cJ and LP/J strains differed significantly in striatal 5-hydroxytryptamine(2A) receptor binding, no marked differences were detected between the phenotypic extremes. A second QTL was detected on chromosome 14 (peak LOD = 6.9), which was located more proximally and included the Chat locus. No QTLs were detected on chromosomes 1 and 9, thus differentiating this cross from previous results obtained for a C57BL/6J x DBA/2J intercross.
Rasmussen
E
E
Department of Psychiatry and Psychology, State University of New York at Stony Brook, Stony Brook, New York, USA.
Cipp
L
L
Hitzemann
R
R
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D002375:Catalepsy / Q000139:chemically induced* / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D016678:Genome; D005838:Genotype; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D019655:Quantitative Trait, Heritable
D014150:Antipsychotic Agents; D006220:Haloperidol