B6;129-Oprm1^tm1.1Cgrf/KffJ

Stock number: 030074
Product name: Oprm1^fl/fl
Research areas: Neurobiology Research, Research Tools

Description

Oprm1^fl/fl mice possess loxP sites flanking exons 2-3 of the opioid receptor, mu 1 (Oprm1) gene. These mice may be useful in studying inflammatory pain control.

Detailed description

Oprm1^fl/fl floxed mice possess loxP sites flanking exons 2-3 of the opioid receptor, mu 1 (Oprm1) gene. μ-opioid receptors (MORs) are G-protein-coupled receptors inhibit neuronal activity upon binding of ligands such as morphine. MORs mediate the powerfull analgesic and addictive properties of opiates. MORs represent the primary target for both clinically used (morphine) and abused (heroin) opiates, and play a role in rewarding effects of drugs of abuse, such as nicotine, cannabinoids and alcohol, as well as natural rewards including social interaction. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2-3 deleted in cre-expressing tissues.

When bred to Nav1.8-Cre mice, expressing Cre Recombinase in peripheral sensory neurons, resulting Mu-cKO mice have a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia. Mu-cKO mice show normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in these mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact.

Development

The Oprm1^fl/fl targeting vector was designed to insert a loxP site upstream of exon 2 and a loxP-flanked hygromycin resistance (hygro) cassette downstream of exon 3 of the opioid receptor, mu 1 (Oprm1) gene. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid to delete the hygro cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exons, intact floxed-hygro cassette, or excision of exons 2-3 and the hygro cassette. Correctly targeted ES cells, containing only the floxed-exons 2-3, were injected into C57BL/6J blastocysts and chimeric males were bred with C57BL/6J females. Resulting Oprm1^fl/fl mice were bred to (C57BL/6J x 129) F1 mice for at least 5 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Oprm1^tm1.1Cgrf
Name: targeted mutation 1.1, Claire Gaveriaux-Ruff
MGI accession ID: MGI:5561219
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Oprm1^fl
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: 129
Molecular note: A loxP site was inserted upstream of exon 2. A floxed hygromycin resistance cassette was inserted downstream of exon 3. Cre-mediated recombination removed the selection cassette and left exons 2 and 3 floxed.