Chromosomal mapping of loci influencing sensitivity to cocaine-induced seizures in BXD recombinant inbred strains of mice.
Among inbred mice, genetic factors mediate differences in sensitivity to the convulsant properties of cocaine; however, the gene(s) underlying cocaine's effects have not been identified. To help elucidate the gene(s) responsible for cocaine seizure susceptibility, we used recombinant inbred-quantitative trait loci (RI-QTL) analyses to identify chromosomal loci associated with cocaine-induced seizures. RI-QTL analyses seek to identify associations between a quantitative measure of a particular phenotype and one or more previously mapped marker genes across a panel of RI strains. This report describes an RI-QTL analysis of cocaine seizure susceptibility among 26 BXD RI strains. These strains showed a skewed, bimodal range of seizure susceptibility which could be the result of one or more modifying genes acting in concert with a major gene to influence cocaine sensitivity. Correlating the percent seizures displayed by each strain following 60 mg/kg cocaine with chromosomal marker data for these strains revealed a number of significant correlations clustered in two regions on chromosomes 12 and 6. This is the first identification of putative chromosomal loci associated with a cocaine-related phenotype and should facilitate identification of the gene(s) underlying cocaine toxicity and other cocaine-related phenotypes.
Miner
L L
LL
Genetics Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Marley
R J
RJ
D000818:Animals; D002874:Chromosome Mapping; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005819:Genetic Markers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D010641:Phenotype; D011995:Recombination, Genetic; D012640:Seizures / Q000139:chemically induced / Q000235:genetics*
D005819:Genetic Markers; D003042:Cocaine