Miner L L, Marley R J
Genetics Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 1995 Jan;117(1):62-6. doi: 10.1007/BF02245099.
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.
在近交系小鼠中，遗传因素介导了对可卡因惊厥特性敏感性的差异；然而，可卡因作用的相关基因尚未被确定。为了帮助阐明导致可卡因癫痫易感性的基因，我们使用重组近交-数量性状位点（RI-QTL）分析来确定与可卡因诱发癫痫相关的染色体位点。RI-QTL分析旨在确定特定表型的定量测量与一组RI品系中一个或多个先前定位的标记基因之间的关联。本报告描述了对26个BXD RI品系可卡因癫痫易感性的RI-QTL分析。这些品系显示出癫痫易感性的偏态双峰范围，这可能是一个或多个修饰基因与一个主要基因协同作用以影响可卡因敏感性的结果。将每个品系在60mg/kg可卡因处理后出现癫痫的百分比与这些品系的染色体标记数据相关联，发现多个显著相关性聚集在12号和6号染色体的两个区域。这是首次鉴定出与可卡因相关表型相关的假定染色体位点，应有助于鉴定可卡因毒性及其他可卡因相关表型的潜在基因。
