Selective Breeding for Ethanol Sensitivity

描述（由申请人提供）：这是一项补充申请，利用1号染色体上高度显著的数量性状基因座（QTL）对高剂量乙醇敏感性的影响，我们在近交系酒精非耐受（IANT）和近交系酒精耐受（IAT）大鼠中发现了该基因座，尽管这些动物是针对低剂量效应选择性繁殖的。该QTL与该表型在近交系高酒精敏感（IHAS）和近交系低酒精敏感（ILAS）大鼠中的一个QTL处于相同的一般位置，但是显著得多并且具有高得多的遗传力。我们将利用这一独特的机会，通过构建QTL的同源菌株，缩小QTL的区域并将结果与I HAS和I LAS大鼠中的相同区域进行比较，来增加我们对乙醇敏感性的了解。我们还在2号和5号染色体上构建来自I HAS和I LAS大鼠的同源品系。IHAS和ILAS大鼠1号染色体上的QTL远小于IANT和IAT大鼠。这些研究很重要，因为人类酒精中毒的风险因素之一是对乙醇的初始敏感性低和/或耐受性迅速发展。我们有两种这种行为的动物模型，选择性饲养的高剂量敏感性大鼠（IHAS和ILAS）和低剂量敏感性动物（IAT和IANT）

DESCRIPTION (provided by applicant): This is a supplemental application to take advantage of a highly significant Quantitative Trait Locus (QTL) on chromosome 1 for high dose ethanol sensitivity that we have discovered in the Inbred Alcohol non- Tolerant (IANT) and the inbred Alcohol Tolerant (IAT rats) in spite of the fact that these animals were selectively bred for low dose effects. This QTL is in the same general location as one for this phenotype in the inbred High Alcohol Sensitive (IHAS) and inbred Low Alcohol Sensitive (ILAS) rats, but is much more significant and has a much higher heritability. We will take advantage of this unique opportunity to add to our knowledge of ethanol sensitivity by construction of congenic strains for the QTL, narrowing the region of the QTL and comparing the results to the same region in the I HAS and I LAS rats. We are also constructing congenic strains from the I HAS and I LAS rats on chromosomes 2 and 5. The QTL on chromosome 1 in the IHAS and ILAS rats is much smaller than in the IANT and IAT rats. These studies are important since among the risk factors for alcoholism in humans is a low initial sensitivity and/or rapid development of tolerance to ethanol. We have two animal models of this behavior, the rats selectively bred for high dose sensitivity (the IHAS and ILAS) and animals bred for low dose sensitivity (the IAT and IANT)