Detection and mapping of quantitative trait loci for haloperidol-induced catalepsy in a C57BL/6J x DBA/2J F2 intercross.

A genomewide scan was conducted to detect quantitative trait loci (QTLs) for haloperidol-induced catalepsy in a C57BL/6J (B6) x DBA/2J (D2) F2 intercross (N = 678). Significant QTLs (LOD, > 4.3) were detected on chromosomes 1 and 9. The relative position of the QTL on chromosome 1 is similar to open-field activity QTLs previously identified by Flint et al. (1995) and Gershenfeld et al. (1997). Given the broad confidence intervals for these QTLs, such associations must be viewed cautiously. However, these data are consistent with the report of Kline et al. (1998), who found a significant genetic associations between catalepsy and open-field activity. The QTL interval on chromosome 9 stretched from approximately 25 to 55 cM; this region contains numerous candidate genes, including Drd2, Ncam, Acat1, and Htr1b. The data also suggest the presence of a second QTL on chromosome 9 (LOD, > 3.5) in the proximal region of the chromosome. Potential candidate genes in this region include Penk2 and Gria4. Overall, these data support our previous observation (Kanes et al., 1996) that for the B6 x D2 genotypes, one or more polymorphisms on chromosome 9 are associated with the variance in haloperidol response.