Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N12+N1F2 (29-SEP-08)   Donating Investigator Brigitte Kieffer,   Université Louis Pasteur Strasbour

Description
Mice homozygous for this kappa-opioid receptor mutant allele (KOR-) are viable and fertile. KOR-selective ligand binding is absent on brain membranes from homozygous mice. In contrast to mutant mice deficient of delta- or mu-opioid receptors (Stock No. 007557 or 007559), KOR- homozygotes have normal mechanical pain thresholds, but greatly increased sensitivity to chemical visceral pain. KOR- homozygotes also exhibit normal spontaneous stress responses (unlike delta-opioid receptor null mice). Homozygous KOR- mice also show decreased ethanol self-administration and decreased THC-conditioned place aversion. These KOR mutant mice may be useful in studying biological activity of opioids, analgesics, spinally mediated thermal nociception and chemical visceral pain thresholds.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. These mutant mice were originally published on a mixed genetic background. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to replace a portion of the first exon (containing the translation initiation codon) of the targeted gene with a PGK-neo cassette. The construct was electroporated into 129S2/SvPas-derived P1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred with C57BL/6 females. These kappa-opioid receptor (KOR) mutant mice were backcrossed to C57BL/6J inbred mice for at least 12 generations prior to arrival at The Jackson Laboratory. The Y chromosome may not have been fixed to the C57BL/6J genetic background.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Oprk1^tm1Kff/Oprk1⁺

        involves: 129S2/SvPas * C57BL/6

• reproductive system phenotype
• increased litter size (MGI Ref ID J:46089)

Oprk1^tm1Kff/Oprk1^tm1Kff

        involves: 129S2/SvPas * C57BL/6

• behavior/neurological phenotype
• abnormal locomotor activity (MGI Ref ID J:46089)
  • failure to decrease locomotor activity following administration of kappa-opioid agonist
• abnormal pain threshold (MGI Ref ID J:46089)
  • increased threshold response to abdominal constriction test
  • failure to raise threshold response in hot plate and tail immersion tests after administration of kappa-opioid agonist
• abnormal response to addictive substance (MGI Ref ID J:46089)
  • attenuated response to morphine withdrawal
• endocrine/exocrine gland phenotype
• decreased salivation (MGI Ref ID J:46089)
  • failure to salivate after administration of kappa-opioid agonist
• reproductive system phenotype
• increased litter size (MGI Ref ID J:46089)
• touch/vibrissae phenotype
• abnormal pain threshold (MGI Ref ID J:46089)
  • increased threshold response to abdominal constriction test
  • failure to raise threshold response in hot plate and tail immersion tests after administration of kappa-opioid agonist
• digestive/alimentary phenotype
• decreased salivation (MGI Ref ID J:46089)
  • failure to salivate after administration of kappa-opioid agonist

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Behavioral and Learning Defects (genes regulating preferences to alcohol)
Receptor Defects (opiod)

Research Tools
Sensorineural Research
Toxicology Research (drug/compound testing)

Sensorineural Research
Nociception

Genes & Alleles

Gene & Allele Information

Allele Symbol		Oprk1tm1Kff
Allele Name		targeted mutation 1, Brigitte L Kieffer
Allele Type		Targeted (knock-out)
Common Name(s)		KOR -; KOR(-); Oprk1-;
Mutation Made By		Brigitte Kieffer,   Université Louis Pasteur Strasbour
Strain of Origin		129S2/SvPas
ES Cell Line Name		P1
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Oprk1, opioid receptor, kappa 1
Chromosome		1
Gene Common Name(s)		KOR; KOR-1; OPRK; Oprk2; R21; opioid receptor, kappa 2;
Molecular Note		Exon 1 was disrupted by the insertion of a neomycin selection cassette. The insertion deleted sequence encoding amino acids 1 through 79. A radiolabeled binding assay demonstrated a lack of endogenous function. [MGI Ref ID J:46089]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Martin M; Matifas A; Maldonado R; Kieffer BL. 2003. Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: distinct mu, delta and kappa tones. Eur J Neurosci 17(4):701-8. [PubMed: 12603260]  [MGI Ref ID J:108005]

Simonin F; Valverde O; Smadja C; Slowe S; Kitchen I; Dierich A; Le Meur M; Roques BP; Maldonado R; Kieffer BL. 1998. Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal. EMBO J 17(4):886-97. [PubMed: 9463367]  [MGI Ref ID J:46089]

Additional References

Oprk1^tm1Kff related

Bigliardi-Qi M; Gaveriaux-Ruff C; Pfaltz K; Bady P; Baumann T; Rufli T; Kieffer BL; Bigliardi PL. 2007. Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings, and itch behavior. J Invest Dermatol 127(6):1479-88. [PubMed: 17185983]  [MGI Ref ID J:121569]

Bruchas MR; Land BB; Aita M; Xu M; Barot SK; Li S; Chavkin C. 2007. Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria. J Neurosci 27(43):11614-23. [PubMed: 17959804]  [MGI Ref ID J:127038]

Cendan CM; Pujalte JM; Portillo-Salido E; Montoliu L; Baeyens JM. 2005. Formalin-induced pain is reduced in sigma(1) receptor knockout mice. Eur J Pharmacol 511(1):73-4. [PubMed: 15777781]  [MGI Ref ID J:101844]

Chefer VI; Czyzyk T; Bolan EA; Moron J; Pintar JE; Shippenberg TS. 2005. Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine. J Neurosci 25(20):5029-37. [PubMed: 15901784]  [MGI Ref ID J:98526]

Clarke S; Czyzyk T; Ansonoff M; Nitsche JF; Hsu MS; Nilsson L; Larsson K; Borsodi A; Toth G; Hill R; Kitchen I; Pintar JE. 2002. Autoradiography of opioid and ORL1 ligands in opioid receptor triple knockout mice. Eur J Neurosci 16(9):1705-12. [PubMed: 12431223]  [MGI Ref ID J:108076]

Contet C; Matifas A; Kieffer BL. 2004. No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse. Eur J Pharmacol 492(2-3):131-6. [PubMed: 15178356]  [MGI Ref ID J:101864]

Garcia-Sevilla JA; Ferrer-Alcon M; Martin M; Kieffer BL; Maldonado R. 2004. Neurofilament proteins and cAMP pathway in brains of mu-, delta- or kappa-opioid receptor gene knock-out mice: effects of chronic morphine administration. Neuropharmacology 46(4):519-30. [PubMed: 14975676]  [MGI Ref ID J:97004]

Gaveriaux-Ruff C; Filliol D; Simonin F; Matthes HW; Kieffer BL. 2001. Immunosuppression by delta-opioid antagonist naltrindole: delta- and triple mu/delta/kappa-opioid receptor knockout mice reveal a nonopioid activity. J Pharmacol Exp Ther 298(3):1193-8. [PubMed: 11504820]  [MGI Ref ID J:126857]

Gaveriaux-Ruff C; Simonin F; Filliol D; Kieffer BL. 2003. Enhanced humoral response in kappa-opioid receptor knockout mice. J Neuroimmunol 134(1-2):72-81. [PubMed: 12507774]  [MGI Ref ID J:119182]

Gendron L; Pintar JE; Chavkin C. 2007. Essential role of mu opioid receptor in the regulation of delta opioid receptor-mediated antihyperalgesia. Neuroscience 150(4):807-17. [PubMed: 17997230]  [MGI Ref ID J:130771]

Ghozland S; Matthes HW; Simonin F; Filliol D; Kieffer BL; Maldonado R. 2002. Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors. J Neurosci 22(3):1146-54. [PubMed: 11826143]  [MGI Ref ID J:127005]

Hough LB; Nalwalk JW; Chen Y; Schuller A; Zhu Y; Zhang J; Menge WM; Leurs R; Timmerman H; Pintar JE. 2000. Improgan, a cimetidine analog, induces morphine-like antinociception in opioid receptor-knockout mice Brain Res 880(1-2):102-8. [PubMed: 11032994]  [MGI Ref ID J:65217]

Jamot L; Matthes HW; Simonin F; Kieffer BL; Roder JC. 2003. Differential involvement of the mu and kappa opioid receptors in spatial learning. Genes Brain Behav 2(2):80-92. [PubMed: 12884965]  [MGI Ref ID J:104908]

Juni A; Klein G; Pintar JE; Kest B. 2007. Nociception increases during opioid infusion in opioid receptor triple knock-out mice. Neuroscience 147(2):439-44. [PubMed: 17544222]  [MGI Ref ID J:124042]

Scherrer G; Befort K; Contet C; Becker J; Matifas A; Kieffer BL. 2004. The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: a parallel study of mu, delta and combinatorial opioid receptor knockout mice. Eur J Neurosci 19(8):2239-48. [PubMed: 15090050]  [MGI Ref ID J:89672]

Slowe SJ; Simonin F; Kieffer B; Kitchen I. 1999. Quantitative autoradiography of mu-,delta- and kappa1 opioid receptors in kappa-opioid receptor knockout mice. Brain Res 818(2):335-45. [PubMed: 10082819]  [MGI Ref ID J:53699]

Sweger EJ; Casper KB; Scearce-Levie K; Conklin BR; McCarthy KD. 2007. Development of hydrocephalus in mice expressing the G(i)-coupled GPCR Ro1 RASSL receptor in astrocytes. J Neurosci 27(9):2309-17. [PubMed: 17329428]  [MGI Ref ID J:119818]

Xu M; Bruchas MR; Ippolito DL; Gendron L; Chavkin C. 2007. Sciatic nerve ligation-induced proliferation of spinal cord astrocytes is mediated by kappa opioid activation of p38 mitogen-activated protein kinase. J Neurosci 27(10):2570-81. [PubMed: 17344394]  [MGI Ref ID J:120111]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities may require a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.