Hall F S, Li X F, Goeb M, Roff S, Hoggatt H, Sora I, Uhl G R
Molecular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD 21224, USA.
Genes Brain Behav. 2003 Apr;2(2):114-21. doi: 10.1034/j.1601-183x.2003.00016.x.
Homozygous mu-opioid receptor (MOR) knockout (KO) mice developed on a chimeric C57B6/129SV background lack morphine-induced antinociception, locomotion and reward. Therefore it appears that MOR largely mediates these morphine actions. However, one factor that could affect the extent of knockout deficits in morphine-induced behavior is the genetic background against which the gene deletion is expressed. To examine the effect of genetic background chimeric C57B6/129SV MOR knockout mice from the 15th generation of those developed in our laboratory were backcrossed for 10 successive generations with C57BL/6 mice, a strain which is more sensitive to many of the properties of morphine, to produce congenic MOR (con-MOR) KO mice. Heterozygote conMOR KO mice display attenuated morphine locomotion and reduced morphine analgesia compared to wild-type mice. Homozygote con-MOR KO mice display baseline hyperalgesia, no morphine place preference, no morphine analgesia and no morphine locomotion. These results are not qualitatively different from those observed in the MOR KO strain with a chimeric C57B6/129SV background, and suggest that although the strain has separate influences on these functions, it does not substantially interact with deletion of the mu opiate receptor gene.
在嵌合C57B6/129SV背景上培育的纯合μ-阿片受体(MOR)敲除(KO)小鼠缺乏吗啡诱导的镇痛、运动和奖赏效应。因此,MOR似乎在很大程度上介导了这些吗啡作用。然而,一个可能影响吗啡诱导行为中敲除缺陷程度的因素是基因缺失所表达的遗传背景。为了研究遗传背景的影响,将我们实验室培育的第15代嵌合C57B6/129SV MOR敲除小鼠与对吗啡的许多特性更敏感的C57BL/6小鼠连续回交10代,以产生同源MOR(con-MOR)敲除小鼠。与野生型小鼠相比,杂合子conMOR敲除小鼠表现出减弱的吗啡诱导运动和降低的吗啡镇痛作用。纯合子con-MOR敲除小鼠表现出基线痛觉过敏、无吗啡位置偏爱、无吗啡镇痛和无吗啡诱导运动。这些结果与在嵌合C57B6/129SV背景的MOR敲除品系中观察到的结果在性质上没有差异,表明尽管该品系对这些功能有单独的影响,但它与μ阿片受体基因的缺失没有实质性的相互作用。