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Chunk #19 — Animal models of 118A>G

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The genetics of the opioid system and specific drug addictions.
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Two mouse models of 118A>G with the equivalent amino acid substitution have been developed using two different approaches. In one model, knock-in mice homozygous for the equivalent (112G) allele (Asn38Asp) exhibited reduced oprm1 mRNA and protein levels in multiple brain regions and sex-specific reductions in the rewarding properties of morphine (Mague et al. 2009). In the second model, two humanized mice lines were produced by introduction of human exon 1 with and without the variant 118G into the mouse gene. Mice bearing the 118GG genotype showed a greater peak of striatal dopamine response to an alcohol challenge (Ramchandani et al. 2011).