Identification of quantitative trait loci for chemical/inflammatory nociception in mice

Identification of quantitative trait loci for chemical/inflammatory nociception in mice
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DOI:
10.1016/s0304-3959(01)00489-4
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发表时间:
2002-04-01
期刊:
影响因子:
7.4
通讯作者:
Mogil, JS
Mogil, JS
中科院分区:
医学1区
文献类型:
--
作者:
Wilson, SG;Chesler, EJ;Mogil, JS

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对疼痛的敏感性有很大的差异,而这种差异很大程度上源于遗传。已经开始确定负责的特定基因,但仅限于热痛觉。为了便于鉴定具有更多临床相关性的多态疼痛相关基因,我们对最常见的炎症伤害感受检测——福尔马林测试——进行了数量性状位点(QTL)定位研究。QTL定位是一种利用自交系之间自然发生的变异来鉴定包含导致这种变异的基因的基因组位置的技术。以自交系A/J和C57BL/6J小鼠为祖鼠,构建F杂交,这两种小鼠先前分别对福尔马林诱导的伤害感受表现出抗性和敏感性。经过表型检测(5%福尔马林,25个足底注射),小鼠在基因组中的90个微卫星标记上进行基因分型。我们在小鼠远端9号和10号染色体上为两个统计上显著的福尔马林测试qtl(遗传与性状变异相关的染色体区域)提供了证据。这些qtl的基因鉴定可能阐明炎症性疼痛个体差异的基础,并导致新的镇痛治疗策略。(C) 2002国际疼痛研究协会。Elsevier Science B.V.版权所有。
Sensitivity to pain is widely variable, and much of this variability is genetic in origin. The specific genes responsible have begun to be identified, but only for thermal nociception. In order to facilitate the identification of polymorphic, pain-related genes with more clinical relevance, we performed quantitative trait locus (QTL) mapping studies of the most common assay of inflammatory nociception, the formalin test. QTL mapping is a technique that exploits naturally occurring variability among inbred strains for the identification of genomic locations containing genes contributing to that variability. An F, intercross was constructed using inbred A/J and C57BL/6J mice as progenitors, strains previously shown to display resistance and sensitivity, respectively, to formalin-induced nociception. Following phenotypic testing (5% formalin, 25 mul intraplantar injection), mice were genotyped at 90 microsatellite markers spanning the genome. We provide evidence for two statistically significant formalin test QTLs - chromosomal regions whose inheritance is associated with trait variability - on distal mouse chromosomes 9 and 10. Identification of the genes underlying these QTLs may illuminate the basis of individual differences in inflammatory pain, and lead to novel analgesic treatment strategies. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.