Quantitative trait loci influencing morphine antinociception in four mapping populations
Quantitative trait loci influencing morphine antinociception in four mapping populations
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DOI：
10.1007/s003350020022
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发表时间：
2001-07-01
期刊：
影响因子：
2.5
通讯作者：
Belknap, JK
中科院分区：
文献类型：
--
作者：
Bergeson, SE;Helms, ML;Belknap, JK
镇痛（疼痛减轻或抗伤害感受）是吗啡给药的经典和临床重要作用，在啮齿动物模型中，对吗啡的敏感性已被证明受到基因型的强烈影响。例如，几项研究报道了在热板测定中不敏感的C57 BL/6（B6）和敏感的DBA/2（D2）近交系小鼠品系之间吗啡抗伤害感受的显著差异。这促使本全基因组范围内的数量性状位点（QTL）的染色体位点的抗伤害感受的影响程度的搜索，通过使用来自B6和D2祖先近交系的四个作图群体。这四个是BXD重组近交系（RI）菌株集、F-2（B6 D2 F（2））群体、从B6 D2 F（2）建立群体中进行抗伤害感受的短期选择性育种以及初期或完成的同类菌株。在BXD RI集合和B6 D2 F（2）中，全基因组搜索以标称p <0.05鉴定了10-12个临时QTL。随后将其他群体用作确认步骤以测试每个临时QTL区域。基于所有可用的作图群体，四个QTL在近端染色体（Chr）1（仅雌性）、近端Chr 9（仅雌性）、中间Chr 9和近端Chr 10上出现为显著的（p < .00005）。Chr 10 QTL与μ阿片受体基因（Oprm）对应于相同的区域;该受体是已知的吗啡的抗伤害感受作用的介体。Chr 1 QTL仅在雌性中明显，并且与K-阿片受体基因Oprk匹配。
Analgesia(pain reduction, or antinociception) is a classical and clinically important effect of morphine administration, and in rodent models sensitivity to morphine has been shown to be strongly influenced by genotype. For example, several studies have reported marked differences in morphine antinociception between the insensitive C57BL/6 (B6) and sensitive DBA/2 (D2) inbred mouse strains on the hot-plate assay. This prompted the present genome-wide search for quantitative trait loci (QTLs) that are chromosomal sites influencing the magnitude of antinociception, by using four mapping populations derived from the B6 and D2 progenitor inbred strains. These four were the BXD recombinant inbred (RI) strain set, an F-2 (B6D2F(2)) population, short-term selective breeding for antinociception from a B6D2F(2) founding population, and incipient or completed congenic strains. In the BXD RI set and in the B6D2F(2), a genome-wide search identified 10-12 provisional QTLs at a nominal p < .05. The other populations were subsequently used as confirmation steps to test each of the provisional QTL regions. Based on all available mapping populations, four QTLs emerged as significant (p < .00005) on proximal Chromosome (Chr) 1 (females only), proximal Chr 9 (females only), mid Chr 9, and proximal Chr 10. The Chr 10 QTL comaps to the same region as the mu -opioid receptor gene (Oprm); this receptor is a known mediator of morphine's antinociceptive effects. The Chr 1 QTL was evident only in females and comapped with the K-opioid receptor gene, Oprk.