Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   05-AUG-09 Species laboratory mouse Generation ?+N12+N1F10 (04-JAN-13) Generation Definitions   Donating Investigator Brigitte L. Kieffer,   Université Louis Pasteur Strasbour

Description
Mice homozygous for this mu-opioid receptor mutant allele (MOR-) are viable and fertile. MOR-selective ligand binding is absent on brain membranes from homozygous mice. Homozygous MOR- mice exhibit a lack of morphine analgesia, reward, and withdrawal. This is accompanied by decreased mechanical, thermal, and chemical pain thresholds. Homozygous MOR- mice also show decreased ethanol self-administration and decreased THC-conditioned place aversion. In contrast to mutant mice deficient of delta- or kappa-opioid receptors (Stock No. 007557 or 007558, respectively), MOR- homozygotes exhibit hypolocomotive spontaneous stress responses. Indeed, the reduced anxiety and depressive-like behavior observed in MOR- mutants is in stark contrast to kappa-opioid receptor deficient mice. These MOR mutant mice may be useful in studying the biological activity of opioids, analgesics, and responses to mechanical, chemical and thermal nociception at a supraspinal level.

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 insert a PGK-neo cassette into exon 2 of the targeted gene. 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 mice were bred with C57BL/6 mice. These mu-opioid receptor (MOR) 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

Related Strains

Strains carrying other alleles of Oprm1

008750

B6.Cg-Tg(Th-Oprm1)4Jtw/J

View Strains carrying other alleles of Oprm1     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Oprm1^tm1Kff/Oprm1^tm1Kff

        129S2/SvPas

• behavior/neurological phenotype
• abnormal pain threshold
  • administration of morphine does not affect threshold response in tail immersion and hot plate tests   (MGI Ref ID J:36241)
  • attenuated response after foot-shock exposure   (MGI Ref ID J:62551)
• decreased behavioral withdrawal response
  • prolonged morphine administration does not create symptoms of dependence or withdrawal   (MGI Ref ID J:62551)
• hypoactivity
  • mild change   (MGI Ref ID J:36241)
• impaired behavioral response to morphine
  • no affect on conditioned place preference induced by morphine no effect on conditioned place preference induced by morphine   (MGI Ref ID J:36241)
  • prolonged morphine administration does not create symptoms of dependence or withdrawal   (MGI Ref ID J:36241)
• increased coping response
  • slightly decreased immobility time in forced-swim test   (MGI Ref ID J:62551)
• integument phenotype
• abnormal pain threshold
  • administration of morphine does not affect threshold response in tail immersion and hot plate tests   (MGI Ref ID J:36241)
  • attenuated response after foot-shock exposure   (MGI Ref ID J:62551)

Oprm1^tm1Kff/Oprm1^tm1Kff

        involves: 129S2/SvPas

• behavior/neurological phenotype
• impaired behavioral response to anesthetic
  • in a tail flick assay, mice treated with morphine-6beta-glucuronide (M6G) or 6-acetyl-morphine exhibit no analgesic response unlike similarly treated wild-type mice   (MGI Ref ID J:52952)
• impaired behavioral response to morphine
  • in a tail flick assay, mice treated with morphine-6beta-glucuronide (M6G) or 6-acetyl-morphine exhibit no analgesic response unlike similarly treated wild-type mice   (MGI Ref ID J:52952)

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
      genes regulating preferences to alcohol and stress
      mu opioid receptor deficiency
Receptor Defects
      opiod

Research Tools
Sensorineural Research
Toxicology Research
      drug/compound testing

Sensorineural Research
Nociception

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Oprm1tm1Kff
Allele Name		targeted mutation 1, Brigitte L Kieffer
Allele Type		Targeted (knock-out)
Common Name(s)		MOR-;
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		Oprm1, opioid receptor, mu 1
Chromosome		10
Gene Common Name(s)		LMOR; M-OR-1; MOP; MOP receptor; MOP-R; MOR; MOR-1; MOR1; MORA; OPRM; Oprrm1; muOR;
Molecular Note		A neomycin selection cassette was inserted into exon 2. Binding assays on brain of homozygous animals confirmed that no functional protein was made from this allele. [MGI Ref ID J:36241]

Genotyping

Genotyping Information

Genotyping Protocols

Oprm1^tm1Kff, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Matthes HW; Maldonado R; Simonin F; Valverde O; Slowe S; Kitchen I; Befort K; Dierich A; Le Meur M; Dolle P; Tzavara E; Hanoune J; Roques BP; Kieffer BL. 1996. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene [see comments] Nature 383(6603):819-23. [PubMed: 8893006]  [MGI Ref ID J:36241]

Additional References

Oprm1^tm1Kff related

Berrendero F; Kieffer BL; Maldonado R. 2002. Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice. J Neurosci 22(24):10935-40. [PubMed: 12486188]  [MGI Ref ID J:91861]

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]

Burbassi S; Sengupta R; Meucci O. 2010. Alterations of CXCR4 function in mu-opioid receptor-deficient glia. Eur J Neurosci 32(8):1278-88. [PubMed: 20880358]  [MGI Ref ID J:169500]

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; Denoroy L; Zapata A; Shippenberg TS. 2009. Mu opioid receptor modulation of somatodendritic dopamine overflow: GABAergic and glutamatergic mechanisms. Eur J Neurosci 30(2):272-8. [PubMed: 19614973]  [MGI Ref ID J:151565]

Chefer VI; Kieffer BL; Shippenberg TS. 2003. Basal and morphine-evoked dopaminergic neurotransmission in the nucleus accumbens of MOR- and DOR-knockout mice. Eur J Neurosci 18(7):1915-22. [PubMed: 14622224]  [MGI Ref ID J:89630]

Chefer VI; Kieffer BL; Shippenberg TS. 2004. Contrasting effects of micro opioid receptor and delta opioid receptor deletion upon the behavioral and neurochemical effects of cocaine. Neuroscience 127(2):497-503. [PubMed: 15262338]  [MGI Ref ID J:91973]

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]

Dahan A; Sarton E; Teppema L; Olievier C; Nieuwenhuijs D; Matthes HW; Kieffer BL. 2001. Anesthetic potency and influence of morphine and sevoflurane on respiration in mu-opioid receptor knockout mice. Anesthesiology 94(5):824-32. [PubMed: 11388534]  [MGI Ref ID J:106575]

Filliol D; Ghozland S; Chluba J; Martin M; Matthes HW; Simonin F; Befort K; Gaveriaux-Ruff C; Dierich A; LeMeur M; Valverde O; Maldonado R; Kieffer BL. 2000. Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet 25(2):195-200. [PubMed: 10835636]  [MGI Ref ID J:62551]

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; Karchewski LA; Hever X; Matifas A; Kieffer BL. 2008. Inflammatory pain is enhanced in delta opioid receptor-knockout mice. Eur J Neurosci 27(10):2558-67. [PubMed: 18513322]  [MGI Ref ID J:137050]

Gaveriaux-Ruff C; Matthes HW; Peluso J; Kieffer BL. 1998. Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. Proc Natl Acad Sci U S A 95(11):6326-30. [PubMed: 9600964]  [MGI Ref ID J:48241]

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]

Ghozland S; Chu K; Kieffer BL; Roberts AJ. 2005. Lack of stimulant and anxiolytic-like effects of ethanol and accelerated development of ethanol dependence in mu-opioid receptor knockout mice. Neuropharmacology 49(4):493-501. [PubMed: 15961126]  [MGI Ref ID J:106610]

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]

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]

Laurent V; Leung B; Maidment N; Balleine BW. 2012. mu- and delta-opioid-related processes in the accumbens core and shell differentially mediate the influence of reward-guided and stimulus-guided decisions on choice. J Neurosci 32(5):1875-83. [PubMed: 22302826]  [MGI Ref ID J:181339]

Lena I; Matthes H; Kieffer B; Kitchen I. 2004. Quantitative autoradiography of dopamine receptors in the brains of micro-opioid receptor knockout mice. Neurosci Lett 356(3):220-4. [PubMed: 15036634]  [MGI Ref ID J:121034]

Majumdar S; Grinnell S; Le Rouzic V; Burgman M; Polikar L; Ansonoff M; Pintar J; Pan YX; Pasternak GW. 2011. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci U S A 108(49):19778-83. [PubMed: 22106286]  [MGI Ref ID J:180448]

Marquez P; Baliram R; Kieffer BL; Lutfy K. 2007. The mu opioid receptor is involved in buprenorphine-induced locomotor stimulation and conditioned place preference. Neuropharmacology 52(6):1336-41. [PubMed: 17367825]  [MGI Ref ID J:124471]

Matthes HW; Smadja C; Valverde O; Vonesch JL; Foutz AS; Boudinot E; Denavit-Saubie M; Severini C; Negri L; Roques BP; Maldonado R; Kieffer BL. 1998. Activity of the delta-opioid receptor is partially reduced, whereas activity of the kappa-receptor is maintained in mice lacking the mu-receptor. J Neurosci 18(18):7285-95. [PubMed: 9736649]  [MGI Ref ID J:120239]

Melief EJ; Miyatake M; Bruchas MR; Chavkin C. 2010. Ligand-directed c-Jun N-terminal kinase activation disrupts opioid receptor signaling. Proc Natl Acad Sci U S A 107(25):11608-13. [PubMed: 20534436]  [MGI Ref ID J:161284]

Morin-Surun MP; Boudinot E; Dubois C; Matthes HW; Kieffer BL; Denavit-Saubie M; Champagnat J; Foutz AS. 2001. Respiratory function in adult mice lacking the mu-opioid receptor: role of delta-receptors. Eur J Neurosci 13(9):1703-10. [PubMed: 11359522]  [MGI Ref ID J:89400]

Nieto MM; Guen SL; Kieffer BL; Roques BP; Noble F. 2005. Physiological control of emotion-related behaviors by endogenous enkephalins involves essentially the delta opioid receptors. Neuroscience 135(2):305-13. [PubMed: 16112476]  [MGI Ref ID J:104438]

Oakley SM; Toth G; Borsodi A; Kieffer BL; Kitchen I. 2003. G-protein coupling of delta-opioid receptors in brains of mu-opioid receptor knockout mice. Eur J Pharmacol 466(1-2):91-8. [PubMed: 12679145]  [MGI Ref ID J:102598]

Olmstead MC; Ouagazzal AM; Kieffer BL. 2009. Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task. PLoS ONE 4(2):e4410. [PubMed: 19198656]  [MGI Ref ID J:146471]

Papaleo F; Kieffer BL; Tabarin A; Contarino A. 2007. Decreased motivation to eat in mu-opioid receptor-deficient mice. Eur J Neurosci 25(11):3398-405. [PubMed: 17553008]  [MGI Ref ID J:126072]

Roberts AJ; McDonald JS; Heyser CJ; Kieffer BL; Matthes HW; Koob GF; Gold LH. 2000. mu-Opioid receptor knockout mice do not self-administer alcohol. J Pharmacol Exp Ther 293(3):1002-8. [PubMed: 10869404]  [MGI Ref ID J:120530]

Robledo P; Mendizabal V; Ortuno J; de la Torre R; Kieffer BL; Maldonado R. 2004. The rewarding properties of MDMA are preserved in mice lacking mu-opioid receptors. Eur J Neurosci 20(3):853-8. [PubMed: 15255997]  [MGI Ref ID J:100339]

Samaco RC; Mandel-Brehm C; McGraw CM; Shaw CA; McGill BE; Zoghbi HY. 2012. Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome. Nat Genet 44(2):206-11. [PubMed: 22231481]  [MGI Ref ID J:181213]

Sanders MJ; Kieffer BL; Fanselow MS. 2005. Deletion of the mu opioid receptor results in impaired acquisition of Pavlovian context fear. Neurobiol Learn Mem 84(1):33-41. [PubMed: 15936681]  [MGI Ref ID J:103799]

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]

Schuller AG; King MA; Zhang J; Bolan E; Pan YX; Morgan DJ; Chang A ; Czick ME ; Unterwald EM ; Pasternak GW ; Pintar JE. 1999. Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1. Nat Neurosci 2(2):151-6. [PubMed: 10195199]  [MGI Ref ID J:52952]

Skoubis PD; Matthes HW; Walwyn WM; Kieffer BL; Maidment NT. 2001. Naloxone fails to produce conditioned place aversion in mu-opioid receptor knock-out mice. Neuroscience 106(4):757-63. [PubMed: 11682161]  [MGI Ref ID J:126648]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous or homozygous mice may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)   05-AUG-09
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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