一两个基因位点介导选择性培育小鼠的高阿片类镇痛作用。

One or two genetic loci mediate high opiate analgesia in selectively bred mice.

作者信息

Mogil Jeffrey S, Marek Przemyslaw, Flodman Pamela, Spence Anne M, Sternberg Wendy F, Kest Benjamin, Sadowski Bogdan, Liebeskind John C

机构信息

Research Service (151W), VA Medical Center, Portland, OR 97201 USA Oregon Health Sciences University, Portland, OR 97201 USA ACEA Pharmaceuticals, Plumwood House 1003, Health Sciences Road West, Irvine, CA 92715 USA Division of Human Genetics and Birth Defects, Department of Pediatrics, University of California at Irvine, Irvine, CA 92717 USA Department of Psychology and Brain Research Institute, University of California at Los Angeles, Los Angeles, CA 90024 USA Department of Behavioural Physiology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec Poland.

出版信息

Pain. 1995 Feb;60(2):125-135. doi: 10.1016/0304-3959(94)00098-Y.

DOI:10.1016/0304-3959(94)00098-Y

PMID:7784097

Abstract

The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice. These lines, which have been selectively bred for more than 25 generations, display markedly divergent opioid-mediated SSIA (3-min swims in 38 degrees C water), morphine analgesia (10 mg/kg, i.p.), and analgesia to the kappa-receptor agonist, U-50,488H (30 mg/kg, i.p.). The present study investigated the mode of inheritance of these opioid analgesias in HA and LA mice, using Mendelian genetic analyses. We report that the differential sensitivity of HA and LA mice to each of these analgesic manipulations appears to be determined oligogenically, by one or at the most two major genetic loci. The loci associated with each type of analgesia do not co-segregate, however, indicating that three distinct oligogenic effects have been identified. These findings suggest that the genetic determination of analgesic mechanisms may have simple components and as such may be amenable to further analysis using molecular genetic techniques.

摘要

人类和实验动物的镇痛反应具有显著的个体差异。这种变异性的遗传基础可以在啮齿动物中通过选择性育种程序进行实验研究。其中一个程序在瑞士韦伯斯特小鼠的热板（56摄氏度）试验中，选择高（HA）和低（LA）游泳应激诱导镇痛（SSIA）的小鼠。这些品系已经选择性繁殖了25代以上，在阿片类药物介导的SSIA（在38摄氏度水中游泳3分钟）、吗啡镇痛（10毫克/千克，腹腔注射）以及对κ受体激动剂U-50,488H（30毫克/千克，腹腔注射）的镇痛方面表现出明显的差异。本研究使用孟德尔遗传分析方法，研究了这些阿片类镇痛作用在HA和LA小鼠中的遗传模式。我们报告，HA和LA小鼠对每种镇痛操作的不同敏感性似乎是由一个或最多两个主要基因位点寡基因决定的。然而，与每种镇痛类型相关的基因位点并不共分离，这表明已经确定了三种不同的寡基因效应。这些发现表明，镇痛机制的遗传决定可能具有简单的成分，因此可能适合使用分子遗传技术进行进一步分析。