Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Robert Messing,   University of California, San Francisco

Description
Mice that are homozygous for the Prkce^tm1Msg targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous females produce small litters (0-2 pups). Protein kinase C, epsilon protein was not immunodetectable in dorsal root ganglia or in the central nervous system of mutant mice. Homozygous mutant mice exhibit reduced anxiety, reduced alcohol consumption and reduced responses to nociceptive stimuli. The mice are also supersensitive to acute behavioral effects of allosteric Gamma aminobutyrate (GABA) type A receptor activating drugs. This strain represents a model that may be useful in studies of pharmacological agents for the treatment of alcoholism, anxiety and pain.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a 1.2 Kb region of the Prkce gene, including the exon encoding the translation initiation codon. The construct was electroporated into 129S4/SvJae derived RF8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.

Control Information

	Control
	Wild-type from the colony
	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.

Prkce^tm1Msg/Prkce^tm1Msg

        involves: 129S4/SvJae * C57BL/6J

• behavior/neurological phenotype
• abnormal liquid preference (MGI Ref ID J:58126)
  • 75% lower alcohol preference compared to wild-type
• abnormal pain threshold (MGI Ref ID J:57887)
  • reduced withdrawal response on the von Frey hair stimulation test following epinephrine administration
• abnormal thermal nociception (MGI Ref ID J:57887)
  • reduced thermal hyperalgesia following epinephrine administration
• decreased anxiety-related response (MGI Ref ID J:79806)
  • increased activity in open field test and elevated maze plus test compared to wild-type, pretreatment with 1.5 mg/kg of bicuculline reduced activity in elevated plus maze test
• decreased chemically-elicited antinociception (MGI Ref ID J:57887)
  • reduced nociceptive score on the acetic acid writhing test
• hyperactivity (MGI Ref ID J:58126)
  • increased locomotor activity following diazepam administration
• hyperactivity elicited by ethanol administration (MGI Ref ID J:58126)
  • 2-fold increase in locomotor activity following ethanol injection
• impaired righting response (MGI Ref ID J:58126)
  • increased duration of regaining ethanol-induced loss or righting response
• increased sensitivity to addictive substance (MGI Ref ID J:58126)
  • increased sensitivity to pentobarbital, 30-fold greater sensitivity to diazepam
• homeostasis/metabolism phenotype
• decreased circulating adrenocorticotropin level (MGI Ref ID J:79806)
• decreased circulating corticosterone level (MGI Ref ID J:79806)
  • reduced serum levels of corticosterone before and after a 10 minute period of restraint
• touch/vibrissae phenotype
• abnormal pain threshold (MGI Ref ID J:57887)
  • reduced withdrawal response on the von Frey hair stimulation test following epinephrine administration
• abnormal thermal nociception (MGI Ref ID J:57887)
  • reduced thermal hyperalgesia following epinephrine administration
• decreased chemically-elicited antinociception (MGI Ref ID J:57887)
  • reduced nociceptive score on the acetic acid writhing test

View Research Applications

Research Applications

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

Prkce^tm1Msg related

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Sensorineural Research
Nociception

Genes & Alleles

Gene & Allele Information

Allele Symbol		Prkcetm1Msg
Allele Name		targeted mutation 1, Robert Messing
Allele Type		Targeted (knock-out)
Common Name(s)		PKC-epsilon-; PKCepsilon-;
Mutation Made By		Robert Messing,   University of California, San Francisco
Strain of Origin		129S4/SvJae
ES Cell Line Name		RF8
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Prkce, protein kinase C, epsilon
Chromosome		17
Gene Common Name(s)		5830406C15Rik; MGC125656; MGC125657; PKCE; PKC[e]; PKCepsilon; Pkce; R75156; RIKEN cDNA 5830406C15 gene; expressed sequence R75156; nPKC-epsilon;
Molecular Note		1.2 kb of this gene including the translation initiation site was deleted via homologous recombination with a neo-derived targeting vector. Western blot indicated homozygous mutant animals did not express protein in dorsal root ganglion. [MGI Ref ID J:57887]

Genotyping

Genotyping Information

Genotyping Protocols

Prkce^tm1Msg, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Khasar SG; Lin YH; Martin A; Dadgar J; McMahon T; Wang D; Hundle B; Aley KO; Isenberg W; McCarter G; Green PG; Hodge CW; Levine JD; Messing RO. 1999. A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. Neuron 24(1):253-60. [PubMed: 10677042]  [MGI Ref ID J:57887]

Additional References

Jin ZQ; Zhou HZ; Zhu P; Honbo N; Mochly-Rosen D; Messing RO; Goetzl EJ; Karliner JS; Gray MO. 2002. Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKC epsilon knockout mouse hearts. Am J Physiol Heart Circ Physiol 282(6):H1970-7. [PubMed: 12003800]  [MGI Ref ID J:77066]

Olive MF; Mehmert KK; Messing RO; Hodge CW. 2000. Reduced operant ethanol self-administration and in vivo mesolimbic dopamine responses to ethanol in PKCepsilon-deficient mice. Eur J Neurosci 12(11):4131-40. [PubMed: 11069609]  [MGI Ref ID J:89422]

Prkce^tm1Msg related

Bajo M; Cruz MT; Siggins GR; Messing R; Roberto M. 2008. Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala. Proc Natl Acad Sci U S A 105(24):8410-5. [PubMed: 18541912]  [MGI Ref ID J:137220]

Barnett M; Lin D; Akoyev V; Willard L; Takemoto D. 2008. Protein kinase C epsilon activates lens mitochondrial cytochrome c oxidase subunit IV during hypoxia. Exp Eye Res 86(2):226-34. [PubMed: 18070622]  [MGI Ref ID J:132507]

Choi DS; Wang D; Dadgar J; Chang WS; Messing RO. 2002. Conditional rescue of protein kinase C epsilon regulates ethanol preference and hypnotic sensitivity in adult mice. J Neurosci 22(22):9905-11. [PubMed: 12427847]  [MGI Ref ID J:80186]

Choi DS; Wang D; Yu GQ; Zhu G; Kharazia VN; Paredes JP; Chang WS; Deitchman JK; Mucke L; Messing RO. 2006. PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice. Proc Natl Acad Sci U S A 103(21):8215-20. [PubMed: 16698938]  [MGI Ref ID J:110206]

Gray MO; Zhou HZ; Schafhalter-Zoppoth I; Zhu P; Mochly-Rosen D; Messing RO. 2004. Preservation of base-line hemodynamic function and loss of inducible cardioprotection in adult mice lacking protein kinase C epsilon. J Biol Chem 279(5):3596-604. [PubMed: 14600145]  [MGI Ref ID J:87583]

Hodge CW; Mehmert KK; Kelley SP; McMahon T; Haywood A; Olive MF; Wang D; Sanchez-Perez AM; Messing RO. 1999. Supersensitivity to allosteric GABA(A) receptor modulators and alcohol in mice lacking PKCepsilon. Nat Neurosci 2(11):997-1002. [PubMed: 10526339]  [MGI Ref ID J:58126]

Hodge CW; Raber J; McMahon T; Walter H; Sanchez-Perez AM; Olive MF; Mehmert K; Morrow AL; Messing RO. 2002. Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cepsilon. J Clin Invest 110(7):1003-10. [PubMed: 12370278]  [MGI Ref ID J:79806]

Jin ZQ; Zhou HZ; Zhu P; Honbo N; Mochly-Rosen D; Messing RO; Goetzl EJ; Karliner JS; Gray MO. 2002. Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKC epsilon knockout mouse hearts. Am J Physiol Heart Circ Physiol 282(6):H1970-7. [PubMed: 12003800]  [MGI Ref ID J:77066]

Kitaura J; Eto K; Kinoshita T; Kawakami Y; Leitges M; Lowell CA; Kawakami T. 2005. Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases. J Immunol 174(8):4495-504. [PubMed: 15814670]  [MGI Ref ID J:98164]

Littler CM; Morris KG Jr; Fagan KA; McMurtry IF; Messing RO; Dempsey EC. 2003. Protein kinase C-epsilon-null mice have decreased hypoxic pulmonary vasoconstriction. Am J Physiol Heart Circ Physiol 284(4):H1321-31. [PubMed: 12505875]  [MGI Ref ID J:83035]

Littler CM; Wehling CA; Wick MJ; Fagan KA; Cool CD; Messing RO; Dempsey EC. 2005. Divergent contractile and structural responses of the murine PKC-epsilon null pulmonary circulation to chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 289(6):L1083-93. [PubMed: 16085670]  [MGI Ref ID J:105000]

Nasser MW; Marjoram RJ; Brown SL; Richardson RM. 2005. Cross-desensitization among CXCR1, CXCR2, and CCR5: role of protein kinase C-epsilon1. J Immunol 174(11):6927-33. [PubMed: 15905535]  [MGI Ref ID J:99016]

Newton PM; Kim JA; McGeehan AJ; Paredes JP; Chu K; Wallace MJ; Roberts AJ; Hodge CW; Messing RO. 2007. Increased response to morphine in mice lacking protein kinase C epsilon. Genes Brain Behav 6(4):329-38. [PubMed: 16899053]  [MGI Ref ID J:137288]

Olive MF; Mehmert KK; Messing RO; Hodge CW. 2000. Reduced operant ethanol self-administration and in vivo mesolimbic dopamine responses to ethanol in PKCepsilon-deficient mice. Eur J Neurosci 12(11):4131-40. [PubMed: 11069609]  [MGI Ref ID J:89422]

Olive MF; Mehmert KK; Nannini MA; Camarini R; Messing RO; Hodge CW. 2001. Reduced ethanol withdrawal severity and altered withdrawal-induced c-fos expression in various brain regions of mice lacking protein kinase C-epsilon. Neuroscience 103(1):171-9. [PubMed: 11311798]  [MGI Ref ID J:125979]

Proctor WR; Poelchen W; Bowers BJ; Wehner JM; Messing RO; Dunwiddie TV. 2003. Ethanol differentially enhances hippocampal GABA A receptor-mediated responses in protein kinase C gamma (PKC gamma) and PKC epsilon null mice. J Pharmacol Exp Ther 305(1):264-70. [PubMed: 12649378]  [MGI Ref ID J:124740]

Qi ZH; Song M; Wallace MJ; Wang D; Newton PM; McMahon T; Chou WH; Zhang C; Shokat KM; Messing RO. 2007. Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. J Biol Chem 282(45):33052-63. [PubMed: 17875639]  [MGI Ref ID J:126967]

Rathore R; Zheng YM; Li XQ; Wang QS; Liu QH; Ginnan R; Singer HA; Ho YS; Wang YX. 2006. Mitochondrial ROS-PKCepsilon signaling axis is uniquely involved in hypoxic increase in [Ca2+]i in pulmonary artery smooth muscle cells. Biochem Biophys Res Commun 351(3):784-90. [PubMed: 17087917]  [MGI Ref ID J:115267]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a C57BL/6J X 129S4 background, and has been backcrossed for 10 generations on a C57BL/6J background. Coat color expected from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	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.

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
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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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.

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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.

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