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与酒精相关行为及中枢神经系统神经降压素指标的常见数量性状基因座:催眠和体温过低效应。

Common quantitative trait loci for alcohol-related behaviors and central nervous system neurotensin measures: hypnotic and hypothermic effects.

作者信息

Erwin V G, Markel P D, Johnson T E, Gehle V M, Jones B C

机构信息

Alcohol Research Center and School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.

出版信息

J Pharmacol Exp Ther. 1997 Feb;280(2):911-8.

PMID:9023306
Abstract

Genetic correlations were found between high-affinity neurotensin receptor (NTR(H)) densities and NT-immunoreactivity (NT-ir) levels in specific brain regions and sensitivity to hypnotic and hypothermic effects of ethanol in LSXSS recombinant inbred strains of mice. Simple sequence length polymorphisms were used to identify quantitative trait loci (QTL) influencing hypnotic and hypothermic sensitivity to ethanol, NTR(H) and low-affinity neurotensin receptor densities and NT-ir levels in LSXSS recombinant inbred strains. Common QTL for NTR(H) receptor densities, NT-ir levels and these ethanol actions were identified. One of the QTL (chromosome 2, 80 cM) for NTR(H) density and hypnotic sensitivity is linked to the NTR(H) gene, Ntsr. Also, QTL for NTR(H) density were found in common with confirmed QTL for hypnotic sensitivity on chromosomes 1 (43 cM), 11 (57 cM) and 15 (56 cM) and with an unconfirmed QTL on chromosome 3 (19 cM). Two common QTL for NT-ir levels, but not NTR(H) or low-affinity neurotensin receptor receptors, and ethanol-induced hypothermia were observed on chromosomes 4 (43 cM) and 6 (41 cM). Two common QTL for NT-ir levels and sleep time were identified on chromosomes 3 (19 cM) and 9 (55 cM). Common QTL indicate that genes regulating NT receptor and/or NT-ir expression may be the same as those regulating sensitivity to ethanol.

摘要

在LSXSS重组近交系小鼠中,发现高亲和力神经降压素受体(NTR(H))密度与特定脑区的神经降压素免疫反应性(NT-ir)水平之间存在遗传相关性,以及与乙醇催眠和体温过低效应的敏感性之间存在遗传相关性。利用简单序列长度多态性来鉴定影响LSXSS重组近交系小鼠对乙醇催眠和体温过低敏感性、NTR(H)和低亲和力神经降压素受体密度以及NT-ir水平的数量性状基因座(QTL)。确定了NTR(H)受体密度、NT-ir水平和这些乙醇作用的共同QTL。其中一个与NTR(H)密度和催眠敏感性相关的QTL(位于2号染色体,80 cM)与NTR(H)基因Ntsr相连。此外,在1号染色体(43 cM)、11号染色体(57 cM)和15号染色体(56 cM)上发现了与已确认的催眠敏感性QTL共同的NTR(H)密度QTL,以及在3号染色体(19 cM)上发现了一个未确认的QTL。在4号染色体(43 cM)和6号染色体(41 cM)上观察到两个共同的NT-ir水平QTL,但不是NTR(H)或低亲和力神经降压素受体的QTL,以及乙醇诱导的体温过低。在3号染色体(19 cM)和9号染色体(55 cM)上鉴定出两个共同的NT-ir水平和睡眠时间QTL。共同的QTL表明,调节NT受体和/或NT-ir表达的基因可能与调节对乙醇敏感性的基因相同。

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