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Congenic C57BL/6 mu opiate receptor (MOR) knockout mice: baseline and opiate effects
1Molecular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD 21224, USA.
Abstract:
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.
Insights
Mice lacking the mu-opioid receptor (MOR) gene show no response to morphine. Creating congenic MOR knockout mice on a C57BL/6 background confirmed that genetic background does not significantly alter these morphine-related behavioral deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- The mu-opioid receptor (MOR) is a primary target for morphine's effects.
- Genetic background can influence the expression of gene knockout phenotypes.
- Previous studies established MOR knockout mice on a chimeric C57B6/129SV background.
Purpose of the Study:
- To investigate the impact of a specific genetic background (C57BL/6) on MOR knockout phenotypes.
- To determine if the C57BL/6 genetic background modifies morphine-induced behaviors in MOR knockout mice.
Main Methods:
- Development of congenic MOR knockout (con-MOR KO) mice by backcrossing chimeric MOR KO mice with C57BL/6 mice for 10 generations.
- Assessment of morphine-induced antinociception, locomotion, and reward behaviors in heterozygote and homozygote con-MOR KO mice compared to wild-type controls.
Main Results:
- Homozygous con-MOR KO mice exhibited baseline hyperalgesia and a complete lack of morphine-induced analgesia, locomotion, and place preference.
- Heterozygous con-MOR KO mice showed reduced morphine analgesia and locomotion compared to wild-type.
- The observed phenotypes in con-MOR KO mice were qualitatively similar to those in the original chimeric MOR KO strain.
Conclusions:
- The C57BL/6 genetic background does not substantially interact with the deletion of the mu-opioid receptor gene.
- While genetic background may have independent influences on these functions, it does not significantly alter the core deficits caused by MOR gene deletion.