Congenic C57BL/6 μ opiate receptor (MOR) knockout mice:: baseline and opiate effects
Congenic C57BL/6 μ opiate receptor (MOR) knockout mice:: baseline and opiate effects
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DOI：
10.1034/j.1601-183x.2003.00016.x
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发表时间：
2003-04-01
影响因子：
2.5
通讯作者：
Uhl, GR
中科院分区：
文献类型：
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作者：
Hall, FS;Li, XF;Uhl, GR
在C57B6/129SV嵌合背景上培育的纯合子MU-阿片受体(MOR)基因敲除(KO)小鼠缺乏吗啡诱导的抗伤害感受、运动和奖赏。因此，似乎MOR在很大程度上调节了这些吗啡的作用。然而，一个可能影响吗啡诱导行为中基因敲除缺陷程度的因素是基因缺失表达的遗传背景。为探讨遗传背景嵌合C57B6/129SV MOR基因敲除小鼠的效应，将本实验室培育的第15代嵌合基因敲除小鼠C57B6/129SV与对吗啡的许多特性更为敏感的C57B6/129SV小鼠回交10代，产生同源MOR(CON-MOR)KO小鼠。与野生型小鼠相比，杂合子ConMOR KO小鼠表现出吗啡运动减弱和吗啡镇痛作用减弱。纯合子ConMOR KO小鼠表现为基线痛敏、无吗啡位置偏爱、无吗啡镇痛、无吗啡运动。这些结果与在具有嵌合C57B6/129SV背景的MOR KO菌株中观察到的结果没有本质上的不同，表明尽管该菌株对这些功能有单独的影响，但它并不实质上与p阿片受体基因的缺失相互作用。
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 conMOR 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 p opiate receptor gene.