RT Journal Article
SR Electronic
T1 Identification of Quantitative Trait Loci for Haloperidol-Induced Catalepsy on Mouse Chromosome 14
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1337
OP 1346
VO 290
IS 3
A1 Erik Rasmussen
A1 Laura Cipp
A1 Robert Hitzemann
YR 1999
UL http://jpet.aspetjournals.org/content/290/3/1337.abstract
AB 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 × LP/J F2 intercross. One thousand thirty-seven F2 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 (χ2 = 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 (χ2 = 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-hydroxytryptamine2A(Htr2a) loci. Although the parental BALB/cJ and LP/J strains differed significantly in striatal 5-hydroxytryptamine2A 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 × DBA/2J intercross. The American Society for Pharmacology and Experimental Therapeutics