Identification of quantitative trait loci for haloperidol-induced catalepsy on mouse chromosome

Erik Rasmussen, Laura Cipp, Robert Hitzemann

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 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-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.

Original languageEnglish (US)
Pages (from-to)1337-1346
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume290
Issue number3
StatePublished - Sep 1 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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