ANALYSIS OF CANDIDATE GENES FOR MORPHINE PREFERENCE QUANTITATIVE TRAIT LOCUS MOP2

被引：12
作者：
Doyle, G. A. [1 ]
Schwebel, C. L. [1 ]
Ruiz, S. E. [1 ]
Chou, A. D. [1 ]
Lai, A. T. [1 ]
Wang, M. -J. [1 ]
Smith, G. G. [1 ,2 ]
Buono, R. J. [3 ]
Berrettini, W. H. [1 ]
Ferraro, T. N. [1 ,3 ]
机构：
[1] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA
[2] Dept Vet Affairs Med Ctr, Res Serv, Coatesville, PA USA
[3] Rowan Univ, Cooper Med Sch, Dept Biomed Sci, Camden, NJ USA
来源：
NEUROSCIENCE | 2014年 / 277卷
基金：
美国国家卫生研究院;
关键词：
mu-opioid receptor; two-bottle choice; Rgs17; Ppp1r14c; IYD; Vip; INBRED MOUSE STRAINS; OPIOID-RECEPTOR GENE; VASOACTIVE INTESTINAL POLYPEPTIDE; NORMAL HUMAN SERUM; PHYSICAL-DEPENDENCE; INDUCED ANALGESIA; RAT-BRAIN; VOLUNTARY CONSUMPTION; CONGENIC STRAINS; MICE LACKING;
D O I：
10.1016/j.neuroscience.2014.07.020
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Compared to DBA/2J (D2), C57BL/6J (B6) inbred mice exhibit strong morphine preference when tested using a two-bottle choice drinking paradigm. A morphine preference quantitative trait locus (QTL), Mop2, was originally mapped to proximal chromosome (Chr) 10 using a B6xD2 F2 intercross population, confirmed with reciprocal congenic strains and fine mapped with recombinant congenic strains. These efforts identified a similar to 10-Million base pair (Mbp) interval, underlying Mop2, containing 35 genes. To further reduce the interval, mice from the D2. B6-Mop2-P1 congenic strain were backcrossed to parental D2 mice and two new recombinant strains of interest were generated: D2.B6-Mop2-P1.pD.dB and D2.B6-Mop2-P1.pD.dD. Results obtained from testing these strains in the two-bottle choice drinking paradigm suggest that the gene(s) responsible for the Mop2 QTL is one or more of 22 remaining within the newly defined interval (similar to 7.6 Mbp) which includes Oprm1 and several other genes related to opioid pharmacology. Real-time qRT-PCR analysis of Oprm1 and opioid-related genes Rgs17, Ppp1r14c, Vip, and Iyd revealed both between-strain and within-strain expression differences in comparisons of saline-and morphine-treated B6 and D2 mice. Analysis of Rgs17 protein levels also revealed both between-strain and within-strain differences in comparisons of saline-and morphine-treated B6 and D2 mice. Results suggest that the Mop2 QTL represents the combined influence of multiple genetic variants on morphine preference in these two strains. Relative contributions of each variant remain to be determined. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：403 / 416
页数：14
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