Confirmation of correlations and common quantitative trait loci between neurotensin receptor density and hypnotic sensitivity to ethanol
Confirmation of correlations and common quantitative trait loci between neurotensin receptor density and hypnotic sensitivity to ethanol
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DOI：
10.1111/j.1530-0277.2001.tb02178.x
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发表时间：
2001-12-01
影响因子：
3.2
通讯作者：
Radcliffe, RA
中科院分区：
文献类型：
--
作者：
Erwin, VG;Gehle, VM;Radcliffe, RA
背景资料：在以前的研究中，观察到对乙醇的催眠敏感性与高亲和力神经降压素受体（NTS 1）结合之间存在遗传相关性。这些性状的临时数量性状基因座（QTL），其中一些QTL被发现在共同的染色体区域。在继续努力检查NTS 1结合能力和催眠敏感性之间的关系，以乙醇，研究旨在确认NTS 1密度之间的相关性在大脑中，乙醇诱导的翻正反射（LORR）的损失的持续时间，并在翻正反射（BECRR）恢复时的血液乙醇浓度。方法：对ILS × ISS F2小鼠和HAS × LAS F2大鼠及其后代进行LORR、BECRR和NTS 1密度的检测。计算LORR和BECRR之间的表型相关性，以及这些测量值与小鼠和大鼠纹状体中NTS 1密度之间的表型相关性。通过使用5个先前报道的LORR QTL的多态性标记对F2小鼠进行基因分型，以确认纹状体、腹侧中脑和额叶皮质中BECRR和NTS 1密度的QTL。LORR和BECRR之间存在表型相关（r = -0.66至-0.74，p < 10（-9））以及这些测量值与小鼠和大鼠纹状体中NTS 1密度之间的关系（r = 0.28-0.38，p < 10（-2））。LORR和BECRR（lod score = 2-6）的QTL位于第1、2和15染色体的共同区域。通过使用来自先前LSXSS RI研究的组合结果和当前结果，在15号染色体上发现了纹状体NTS 1受体密度的约60 cM（lod得分= 3.1），与15号染色体LORR/BECRR QTL在同一区域。结果与先前报道的小鼠NTS 1受体密度和对乙醇催眠敏感性的相关性和QTL一致，将这些相关性扩展到另一个物种，老鼠。这些发现支持NTS 1在乙醇催眠敏感性的遗传介导差异中的作用。
Background: In previous studies, genetic correlations were observed between hypnotic sensitivity to ethanol and high-affinity neurotensin receptor (NTS1) binding. Provisional quantitative trait loci (QTLs) were identified for these traits, and some of these QTLs were found on common chromosomal regions. In continued efforts to examine the relationship between NTS1 binding capacity and hypnotic sensitivity to ethanol, studies were designed to confirm correlations between NTS1 densities in the brain, duration of ethanol-induced loss of righting reflex (LORR), and blood ethanol concentrations at regain of righting reflex (BECRR). Another purpose of the study was to confirm QTLs for these traits.Methods: ILS X ISS F2 mice and HAS X LAS F2 rats as well as the progenitors were tested for LORR, BECRR, and NTS1 densities. Phenotypic correlations were calculated between LORR and BECRR and between these measures and NTS1 densities in striatum from both mice and rats. The F2 mice were genotyped by using polymorphic markers for five previously reported QTLs for LORR to confirm QTLs for BECRR and NTS1 densities in striatum, ventral midbrain, and frontal cortex.Results: Phenotypic correlations were found between LORR and BECRR (r = -0.66 to -0.74, p < 10(-9)) and between these measures and NTS1 densities in striatum (r = 0.28-0.38, p < 10(-2)) from both mice and rats. QTLs for LORR and BECRR (lod score = 2-6) were found in common regions of chromosomes 1, 2, and 15. By using the combined results from a previous LSXSS RI study and the current results, a suggestive QTL (lod score = 3.1) for striatal NTS1 receptor densities was found on chromosome 15 at approximately 60 cM, in the same region as the chromosome 15 LORR/BECRR QTL.Conclusions: The results are in agreement with previously reported correlations and QTLs for NTS1 receptor densities and measures of hypnotic sensitivity to ethanol in mice and extend those correlations to another species, the rat. These findings support a role for NTS1 in genetically mediated differences in hypnotic sensitivity to ethanol.