INBRED AND RECOMBINANT INBRED STRAIN COMPARISONS AND BIOCHEMICAL CORRELATES

近交系和重组近交系比较及生化相关性

• 批准号: 5201672
• 负责人: L MINER
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201672
• 关键词: behavioral genetics; cocaine; drug abuse; genetic mapping; inbreeding; laboratory mouse; pharmacogenetics; phenotype; psychomotor function; stimulant /agonist

There are large individual differences among humans and animals in behavioral, physiological and toxicological responses to drugs of abuse. These individual differences in behavioral responses to drugs also display substantial genetic and environmental influences, are continuously distributed, and appear to be influenced by many genes rather than one or two major genes. For these reasons, application of several of the techniques of genetics and molecular biology could be helpful in identification of genetic influences in readily-studied experimental animals that could shed light on human interindividual differences, and identify genes potentially responsible for behavioral variation in drug responses in these animals. Recombinant inbred strains have been tested for cocaine-induced locomotor responses, sensitization and F2 mice to identify gene loci associated with these phenotypes. Animals from a heterogenous stock have been tested for cocaine-induced locomotor activation, and have been used to establish a genetic selection paradigm to ask if selection for cocaine-induced locomotion also selects for other cocaine-induced functions, including psychomotor stimulant conditioned place preference measures. Each of these approaches will allow improved assessment of genetic influences in substance abuse, and analyses of the recombinant inbred strain comparisons will allow chromosomal mapping of specific genes contributing to the strain differences through quantitative trait locus approaches.

人类和动物之间存在很大的个体差异， 对滥用药物的行为、生理和毒理反应。 对药物的行为反应的个体差异也 表现出巨大的遗传和环境影响，是 连续分布，似乎受到许多基因的影响 而不是一两个主要基因。 因此，应用 遗传学和分子生物学的一些技术可以 有助于识别遗传影响， 可以揭示人类个体间关系的实验动物 差异，并确定可能负责行为的基因 这些动物中药物反应的变化。 重组近交系已被测试可卡因诱导的运动 反应，致敏和F2小鼠，以确定相关的基因位点 这些表型。 来自异种的动物已经被 测试可卡因诱导的运动激活，并已用于 建立一个遗传选择的范例， 可卡因引起的运动也选择其他可卡因引起的运动。 功能，包括精神兴奋剂条件位置偏好 措施 这些方法中的每一种都将有助于改进对 药物滥用中的遗传影响，以及重组 近交系比较将允许特定的染色体作图 通过数量性状导致品系差异的基因 轨迹接近。