B6.Cg-Oprm1^tm1.1Jbwa/J

Stock number: 026221
Product name: MOR KI T394A
Research areas: Neurobiology Research

Description

MOR KI mice contain a mutation in the Oprm1 gene which makes them useful for studying the development of opioid tolerance, addiction, and physical dependence.

Detailed description

MOR KI mice contain the amino acid mutation T394A in exon 4 of the opioid receptor, mu 1 (Oprm1) gene. These receptors are expressed throughout the neocortex, thalamus, nucleus accumbens, hippocampus, and amygdala, as well as in the peripheral nervous system, and have been associated with pain sensitivity. The MOR also has an important role in dependence to drugs of abuse, such as opioid, nicotine, cocaine, and alcohol via its modulation of the dopamine system. Binding of these drugs increases the release of beta-endorphins, which subsequently increase release of dopamine and stimulates cravings. T394 of the MOR is a crucial residue for initiation of agonist-induced opioid receptor phosphorylation. Homozygotes are viable and fertile. This mutation alters opioid tolerance and vulnerability to opioid abuse and dependence. Mice exhibit attenuated opioid tolerance, enhanced vulnerability to heroin self-administration, enhanced brain dopamine response to heroin, and enhanced opioid withdrawal.

Development

A targeting construct was designed to insert a loxP and frt-flanked neomycin (neo) resistance cassette downstream of exon 4 of the opioid receptor, mu 1 (Oprm1) gene. An A to G point mutation was introduced in exon 4, resulting in the amino acid mutation T394A. This targeting construct was electroporated into (C57BL/6N x 129S6/SvEvTac)F1-derived iTL BA1 embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to C57BL/6 females. Offspring were bred to 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J mice (Stock No. 003946) to remove the floxed selection cassette, and progeny were crossed to remove the FLP-expressing transgene. MOR KI mice were bred to C57BL/6 mice for at least 6 generations (please see SNP note below). Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6 ; C57BL/6N genetic background.

Allele

Symbol: Oprm1^tm1.1Jbwa
Name: targeted mutation 1.1, Jia Bei Wang
MGI accession ID: MGI:5586574
Generation method: Targeted
Attributes: Not Specified
Synonyms: MOR KI; T394A
Marker symbol: Oprm1
Marker name: opioid receptor, mu 1
Marker synonyms: LMOR; MOP; MOP receptor; MOP-R; mor; MOR1; M-OR-1; MOR-1; MORA; muOR; Oprm; Oprrm1
Chromosome: 10
Strain of origin: (C57BL/6NTac x 129S6/SvEvTac)F1
Molecular note: A targeting construct was designed to insert a loxP and frt-flanked neomycin (neo) resistance cassette downstream of exon 4 of the opioid receptor, mu 1 (Oprm1) gene. An A to G point mutation was introduced in exon 4, resulting in the amino acid mutation T394A. Flp-mediated recombination removed the FRT-flanked neomycin cassette.