KOR-Cre knock-in/knock-out mice have the endogenous kappa opioid receptor promoter/enhancer sequences directing expression of Cre recombinase. These mice are a Cre-lox tool allowing Cre recombination in Oprk1-expressing cells/tissues (including neurons of the cortex and striatum, retina, lung, liver, and kidney), and may be useful in studying reward, pain, and nociception.
Sarah E Ross, University of Pittsburgh
The Oprk1 gene encodes the kappa opioid receptor, which has numerous important roles in the nervous system including the modulation of mood, reward, pain, and nociception, and is also expressed in some non-neruonal tissues including the heart, liver and lungs.
These KOR-Cre knock-in/knock-out mice (also called Oprk1-Cre) have a Cre recombinase gene inserted into the second exon of the Oprk1 gene, disrupting expression of the endogenous gene. This allele is designed to have the endogenous Oprk1 promoter/enhancer elements directing Cre expression in all cells which typically express kappa opioid receptors.
For example, when crossed to LSL-tdTomato reporter mice (Ai14, Stock No. 007914), fluorescent cells can be detected in the heart, lungs, eyes, and dorsal root ganglia as early as embryonic day 14.5 (E14.5). In the adult brain, fluorescently labeled cells can be observed in the cortex, nucleus accumbens, substantia nigra, striatum, and retina, as well as in the kidney and adrenal glands (Cai et al. 2016).
The KOR-Cre knock-in/knock-out allele (also called Oprk1-Cre) was created in the laboratory of Dr. Sarah E. Ross (University of Pittsburgh). First, a targeting vector was designed to replace exon 2 of the opioid receptor, kappa 1 locus (Oprk1) on chromosome 1 with Cre recombinase followed by an FRT-flanked PGK-neo cassette. The construct was electroporated into 129S4/SvJae-derived J1 ES cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric mice were bred with C57BL/6NCrl mice for germline transmission. The resulting KOR-Cre line was subsequently crossed to a FLP-recombinase expressing strain to remove the FRT-flanked neo, and was then backcrossed to C57BL/6NCrl mice for at least 4 generations prior to sending males to The Jackson Laboratory Repository in 2020. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).
|Allele Name||targeted mutation 1.1, Sarah Ross|
|Allele Type||Targeted (Recombinase-expressing)|
|Gene Symbol and Name||Oprk1, opioid receptor, kappa 1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||The coding region of the gene in exon 2 was replaced with a Cre recombinase gene followed by a polyadenylation sequence. An Frt-flanked neomycin selection cassette was inserted at the 3' end, but removed by flp-mediated recmobination in the final allele.|
Both heterozygous and homozygous mice are viable and fertile with normal breeding, and no reported gross phenotypic or behavioral abnormalities.
When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304).
Alternatively, homozygous mice may be bred together.
When using the KOR-cre mouse strain in a publication, please cite the originating article(s) and include JAX stock #035045 in your Materials and Methods section.
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