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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote (Female x Male) Species laboratory mouse Donating Investigator Brigitte 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 | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Congenic Nomenclature
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.
Oprm1tm1Kff/Oprm1tm1Kff
129S2/SvPas
- behavior/neurological phenotype
- abnormal pain threshold (MGI Ref ID J:36241)
- administration of morphine does not affect threshold response in tail immersion and hot plate tests
- attenuated response after foot-shock exposure
- abnormal response to addictive substance (MGI Ref ID J:36241)
- prolonged morphine administration does not create symptoms of dependence or withdrawal
- no affect on conditioned place preference induced by morphine
- hypoactivity (MGI Ref ID J:36241)
- mild change
- increased coping response (MGI Ref ID J:62551)
- slightly decreased immobility time in forced-swim test
- touch/vibrissae phenotype
- abnormal pain threshold (MGI Ref ID J:36241)
- administration of morphine does not affect threshold response in tail immersion and hot plate tests
- attenuated response after foot-shock exposure
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 and stress)
Behavioral and Learning Defects (genes regulating preferences to alcohol)
Behavioral and Learning Defects (mu opioid receptor deficiency)
Receptor Defects (opiod)
Research Tools
Sensorineural Research
Toxicology Research (drug/compound testing)
Sensorineural Research
Nociception
| 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) | KIAA0403; MOP receptor; MOP-R; MOR; MOR-1; MOR1; MORA; OPRM; 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 Protocols
Oprm1tm1Kff, STD PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
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]
Oprm1tm1Kff relatedBerrendero 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]
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; 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]
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]
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]
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]
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]
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]
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]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous or homozygous mice may be bred. Mating System Heterozygote x Heterozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Oprm1tm1Kff *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $472.80 Heterozygous for Oprm1tm1Kff x Heterozygous for Oprm1tm1Kff
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Oprm1tm1Kff *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $614.70 Heterozygous for Oprm1tm1Kff x Heterozygous for Oprm1tm1Kff
| Supply Notes |
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| 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 |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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. | ||
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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