C57BL/6N-Oprm1^tm1.1Ics/KffJ

Stock number: 035787
Product name: MOR^Venus
Research areas: Neurobiology Research, Research Tools

Description

MOR^Venus reporter mice have the opioid receptor, mu 1 (Oprm1) gene driving expression of a Venus yellow fluorescent protein. These mice may be useful as a means for visualizing receptor neuroanatomy and real-time receptor trafficking in live neurons.

Detailed description

MOR^Venus/Venus mice have a Venus yellow fluorescent protein sequence knocked into the last exon of the opioid receptor, mu 1 (Oprm1) gene, allowing this strain to express endogenous Oprm1-encoded receptors with a fused Venus at the C-terminus. Mice homozygous for this allele are viable and fertile. μ-opioid receptors (MORs) are G-protein-coupled receptors that inhibit neuronal activity upon binding of ligands such as morphine. MORs mediate the powerful 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 emit Venus fluorescence in dorsal root ganglia (DRG) neurons in the brain. Affinity of the receptor for agonists and endogenous peptides is unchanged. Treatment with some MOR agonists, such as Met-Enk and DAMGO, triggers receptor internalization, but not with others such as PZM21 and buprenorphine. Morphine-induced analgesia and hyperlocomotion are unchanged in mutant mice, indicating that the MOR^Venus receptor is fully functional. Venus can be detected by direct fluorescence and by immunohistochemical means.

The donating investigator provided images of MOR-Venus homozygous mouse brain showing anti-GFP amplified Venus fluorescence in habenula [view image] as well as striosomes of the striatum [view image].

Of note, MOR-mCherry (Stock No. 029013) is a similar strain expressing mCherry red fluorescent protein in MOR expressing tissues.

Development

The MOR^Venus targeting vector was designed to insert Venus yellow fluorescent protein cDNA into exon 4 of the opioid receptor, mu 1 (Oprm1) gene, and the endogenous STOP codon was replaced with a 5aa linker. A self-excising loxP-flanked cassette, containing a neomycin resistance (neo) cassette and a frt-flanked protamine-cre, was placed downstream. The construct was electroporated into C57BL/6N-derived embryonic stem (ES) cells and correctly targeted ES cells were transiently transfected with a FLP expression plasmid to delete the neo cassette. Resulting ES cells were injected into recipient BALB/c blastocysts. Subsequently, cre recombinase activity deleted the self-excising cassette and MOR^Venus mice were bred to C57BL/6NCrl mice for 6 generation. Cryopreserved sperm was shipped to The Jackson Laboratory. Upon arrival, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304) to establish our live colony.

Allele

Symbol: Oprm1^tm1.1Ics
Name: targeted mutation 1.1, Mouse Clinical Institute
MGI accession ID: MGI:6469457
Generation method: Targeted
Attributes: Reporter
Synonyms: MOR-Venus; Oprm1^Venus
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/6N
Site of expression: Dorsal root ganglia (DRG) neurons in the brain
Molecular note: The targeting vector is designed to insert Venus yellow fluorescent protein cDNA into exon 4 and replace the endogenous STOP codon with a 5aa linker. A self-excising loxP-flanked cassette, containing a neomycin resistance (neo) cassette and a FRT-flanked protamine-cre, was placed downstream.