Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation F42 (20-JAN-09)   Donating Investigator Susumu Tonegawa,   Massachusetts Institute of Technology

Appearance
white-bellied agouti
Related Genotype: A^w/A^w

Description
Mice homozygous for the Prkcc^tm1Stl targeted mutation are viable and develop normally. Homozygous mice show diminished long-term potentiation (LTP) in the hippocampus, but two other types of synaptic plasticities are normal, namely long-term depression and paired-pulse facilitation. Despite this diminished LTP capacity homozygotes can learn to do hippocampus-dependant tasks, such as the Morris water maze and context-dependent fear conditioning, with only slight deficits.

Development
The Prkcc deficient strain was developed in the lab of Dr. Susumu Tonegawa at the Center for Cancer Research at the Massachusetts Institute of Technology. The 129-derived E14 ES cell line was used.

Control Information

	Control
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Prkcc^tm1Stl/Prkcc^tm1Stl

        involves: 129P2/OlaHsd * C57BL/6

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:16392)
  • normal behavior
  • normal cued conditioning
• abnormal contextual conditioning behavior (MGI Ref ID J:16391)
  • moderate deficit compared to controls
• abnormal spatial learning (MGI Ref ID J:16391)
  • mild deficit in random platform Morris water maze task, deficit overcome with intensive training, however
  • normal spatial learning in both the visible- and hidden-platform Morris water mazes
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:16392)
  • normal paired-pulse facilitation
  • normal long term depression
  • normal brain anatomy
  • normal baseline synaptic transmission in hippocampal CA1 pyrimidal cells
• reduced long term potentiation (MGI Ref ID J:16392)

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

Prkcc^tm1Stl/Prkcc^tm1Stl

        involves: 129P2/OlaHsd * BALB/c

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:16391)
  • normal spatial learning in Morris water maze tasks, relative to controls of same genetic background
  • normal contextual conditioning relative to controls of same genetic background

Prkcc^tm1Stl/Prkcc^tm1Stl

        Background Not Specified

• behavior/neurological phenotype
• abnormal nociception after inflammation (MGI Ref ID J:25061)
  • attenuated response during the second, prolonged phase of nociceptive pain after formalin-injection into paw
• abnormal pain threshold (MGI Ref ID J:25061)
  • failed to develop neuropathic pain (induced by thermal or mechanical means) after partial sciatic nerve section
  • reduced neurochemical changes in the spinal cord after nerve injury
  • normal response to acute pain (thermal or mechanical) stimuli in the absence of nerve injury
• impaired behavioral response to alcohol (MGI Ref ID J:25061)
  • reduced sensitivity to ethanol on loss of righting reflex and hypothermia
  • no such alterations in sensitivity to flunitrazepam or pentobarbital
• immune system phenotype
• decreased inflammatory response (MGI Ref ID J:25061)
  • reduced plasma extravasation in response to intradermal capsaicin injection in the paw
• touch/vibrissae phenotype
• abnormal nociception after inflammation (MGI Ref ID J:25061)
  • attenuated response during the second, prolonged phase of nociceptive pain after formalin-injection into paw
• abnormal pain threshold (MGI Ref ID J:25061)
  • failed to develop neuropathic pain (induced by thermal or mechanical means) after partial sciatic nerve section
  • reduced neurochemical changes in the spinal cord after nerve injury
  • normal response to acute pain (thermal or mechanical) stimuli in the absence of nerve injury

Prkcc^tm1Stl/Prkcc^tm1Stl

        involves: 129X1/SvJ * C57BL/6J

• behavior/neurological phenotype
• enhanced behavioral response to alcohol (MGI Ref ID J:54243)
  • lack of tolerance to sedative-hypnotic effects of chronic (10 day) ethanol diet
  • failed to develop chronic hypothermia tolerance after 10 day ethanol diet

Prkcc^tm1Stl/Prkcc^tm1Stl

        involves: 129S6/SvEvTac * C57BL/6J

• behavior/neurological phenotype
• abnormal behavior (MGI Ref ID J:79995)
  • greater behavioral impulsivity in appetitive-signaled nosepoke test
• alcohol preference (MGI Ref ID J:79995)
  • ingested more ethanol than controls, but no greater consumption of liquid volume
  • while both males and females consumed more ethanol than controls, females consumed more than males
• decreased anxiety-related response (MGI Ref ID J:64043)
  • in elevated plus-maze, black/white box, and mirrored chamber
  • baseline locomotor activity is similar to controls
• impaired behavioral response to alcohol (MGI Ref ID J:54243)
  • lack of tolerance to sedative-hypnotic effects of chronic (10 day) ethanol diet
  • developed chronic hypothermia tolerance after 10 day ethanol diet
• taste/olfaction phenotype
• *normal* taste/olfaction phenotype (MGI Ref ID J:79995)
  • saccharin preference similar to controls
  • nicotine consumption similar to controls

Prkcc^tm1Stl/Prkcc^tm1Stl

        B6.129-Prkcc^tm1Stl

• behavior/neurological phenotype
• enhanced behavioral response to alcohol (MGI Ref ID J:54243)
  • developed tolerance to sedative-hypnotic effects of chronic (10 day) ethanol diet
  • developed chronic hypothermia tolerance after 10 day ethanol diet

View Research Applications

Research Applications

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

Prkcc^tm1Stl related

Neurobiology Research
Behavioral and Learning Defects
Cortical Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Prkcctm1Stl
Allele Name		targeted mutation 1, Susumu Tonegawa
Allele Type		Targeted (knock-out)
Common Name(s)		PKCgamma-KO;
Mutation Made By		Susumu Tonegawa,   Massachusetts Institute of Technology
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Prkcc, protein kinase C, gamma
Chromosome		7
Gene Common Name(s)		MGC105487; MGC57564; PKC; PKC-gamma; PKCC; PKCG; PKCI; PKCgamma; Pkcc; Prkc; RATPKCI; SCA14;
Molecular Note		A neomycin resistance cassette replaced 2.5kb of sequence containing the exon that encodes the nucleotide binding domain. Northern blot analysis of total brain RNA demonstrated that homozygous mutant mice lack normal transcripts. Western blot analysis of total brain protein did not detect the protein in homozygous mutant mice. [MGI Ref ID J:16392]

Genotyping

Genotyping Information

Genotyping Protocols

Pkcc^tm1Stl, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Abeliovich A; Chen C; Goda Y; Silva AJ; Stevens CF; Tonegawa S. 1993. Modified hippocampal long-term potentiation in PKC gamma-mutant mice. Cell 75(7):1253-62. [PubMed: 8269509]  [MGI Ref ID J:16392]

Additional References

Abeliovich A; Paylor R; Chen C; Kim JJ; Wehner JM; Tonegawa S. 1993. PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning. Cell 75(7):1263-71. [PubMed: 8269510]  [MGI Ref ID J:16391]

Harris RA; McQuilkin SJ; Paylor R; Abeliovich A; Tonegawa S; Wehner JM. 1995. Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors [see comments] Proc Natl Acad Sci U S A 92(9):3658-62. [PubMed: 7731960]  [MGI Ref ID J:25061]

Martin WJ; Malmberg AB; Basbaum AI. 2001. PKCgamma contributes to a subset of the NMDA-dependent spinal circuits that underlie injury-induced persistent pain. J Neurosci 21(14):5321-7. [PubMed: 11438608]  [MGI Ref ID J:70174]

Prkcc^tm1Stl related

Abeliovich A; Paylor R; Chen C; Kim JJ; Wehner JM; Tonegawa S. 1993. PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning. Cell 75(7):1263-71. [PubMed: 8269510]  [MGI Ref ID J:16391]

Bowers BJ; Collins AC; Tritto T; Wehner JM. 2000. Mice lacking PKC gamma exhibit decreased anxiety Behav Genet 30(2):111-21. [PubMed: 10979601]  [MGI Ref ID J:64043]

Bowers BJ; Owen EH; Collins AC; Abeliovich A; Tonegawa S; Wehner JM. 1999. Decreased ethanol sensitivity and tolerance development in gamma-protein kinase C null mutant mice is dependent on genetic background. Alcohol Clin Exp Res 23(3):387-97. [PubMed: 10195808]  [MGI Ref ID J:54243]

Bowers BJ; Wehner JM. 2001. Ethanol consumption and behavioral impulsivity are increased in protein kinase Cgamma null mutant mice. J Neurosci 21(21):RC180. [PubMed: 11606660]  [MGI Ref ID J:79995]

Celerier E; Simonnet G; Maldonado R. 2004. Prevention of fentanyl-induced delayed pronociceptive effects in mice lacking the protein kinase Cgamma gene. Neuropharmacology 46(2):264-72. [PubMed: 14680764]  [MGI Ref ID J:97025]

Chen C; Kano M; Abeliovich A; Chen L; Bao S; Kim JJ; Hashimoto K; Thompson RF; Tonegawa S. 1995. Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKC gamma mutant mice. Cell 83(7):1233-42. [PubMed: 8548809]  [MGI Ref ID J:31211]

Gardell LR; Ibrahim M; Wang R; Wang Z; Ossipov MH; Malan TP Jr; Porreca F; Lai J. 2004. Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain. Neuroscience 123(1):43-52. [PubMed: 14667440]  [MGI Ref ID J:93597]

Harris RA; McQuilkin SJ; Paylor R; Abeliovich A; Tonegawa S; Wehner JM. 1995. Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors [see comments] Proc Natl Acad Sci U S A 92(9):3658-62. [PubMed: 7731960]  [MGI Ref ID J:25061]

Hix DM; Bowers BJ; Miyamoto JH; Wehner JM. 2003. Open field activity and EtOH activation of gamma-PKC null mutants. Addict Biol 8(4):399-412. [PubMed: 14690876]  [MGI Ref ID J:146719]

Ji Z; Ebralidze A; Tonegawa S; Vogel MW. 1996. Spinocerebellar mossy fiber terminal topography in the NR2C/PKC gamma double mutant cerebellum. Brain Res Dev Brain Res 97(1):138-42. [PubMed: 8946062]  [MGI Ref ID J:36597]

Kano M; Hashimoto K; Chen C; Abeliovich A; Aiba A; Kurihara H; Watanabe M; Inoue Y; Tonegawa S. 1995. Impaired synapse elimination during cerebellar development in PKC gamma mutant mice. Cell 83(7):1223-31. [PubMed: 8548808]  [MGI Ref ID J:31210]

Kimpo RR; Raymond JL. 2007. Impaired motor learning in the vestibulo-ocular reflex in mice with multiple climbing fiber input to cerebellar Purkinje cells. J Neurosci 27(21):5672-82. [PubMed: 17522312]  [MGI Ref ID J:143017]

Lin D; Barnett M; Lobell S; Madgwick D; Shanks D; Willard L; Zampighi GA; Takemoto DJ. 2006. PKCgamma knockout mouse lenses are more susceptible to oxidative stress damage. J Exp Biol 209(Pt 21):4371-8. [PubMed: 17050852]  [MGI Ref ID J:124716]

Malmberg AB; Chen C; Tonegawa S; Basbaum AI. 1997. Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma [see comments] Science 278(5336):279-83. [PubMed: 9323205]  [MGI Ref ID J:43458]

Martin WJ; Malmberg AB; Basbaum AI. 2001. PKCgamma contributes to a subset of the NMDA-dependent spinal circuits that underlie injury-induced persistent pain. J Neurosci 21(14):5321-7. [PubMed: 11438608]  [MGI Ref ID J:70174]

Narita M; Aoki T; Ozaki S; Yajima Y; Suzuki T. 2001. Involvement of protein kinase Cgamma isoform in morphine-induced reinforcing effects. Neuroscience 103(2):309-14. [PubMed: 11246146]  [MGI Ref ID J:126193]

Narita M; Mizoguchi H; Suzuki T; Narita M; Dun NJ; Imai S; Yajima Y; Nagase H; Suzuki T; Tseng LF. 2001. Enhanced mu-opioid responses in the spinal cord of mice lacking protein kinase Cgamma isoform. J Biol Chem 276(18):15409-14. [PubMed: 11278552]  [MGI Ref ID J:124692]

Ohsawa M; Narita M; Mizoguchi H; Cheng E; Tseng LF. 2001. Reduced hyperalgesia induced by nerve injury, but not by inflammation in mice lacking protein kinase C gamma isoform. Eur J Pharmacol 429(1-3):157-60. [PubMed: 11698038]  [MGI Ref ID J:102599]

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]

Schrenk K; Kapfhammer JP; Metzger F. 2002. Altered dendritic development of cerebellar Purkinje cells in slice cultures from protein kinase Cgamma-deficient mice. Neuroscience 110(4):675-89. [PubMed: 11934475]  [MGI Ref ID J:126191]

Shutoh F; Katoh A; Ohki M; Itohara S; Tonegawa S; Nagao S. 2003. Role of protein kinase C family in the cerebellum-dependent adaptive learning of horizontal optokinetic response eye movements in mice. Eur J Neurosci 18(1):134-42. [PubMed: 12859346]  [MGI Ref ID J:89565]

Wang S; Lim G; Zeng Q; Sung B; Yang L; Mao J. 2005. Central glucocorticoid receptors modulate the expression and function of spinal NMDA receptors after peripheral nerve injury. J Neurosci 25(2):488-95. [PubMed: 15647493]  [MGI Ref ID J:97679]

Yevseyenkov VV; Das S; Lin D; Willard L; Davidson H; Sitaramayya A; Giblin FJ; Dang L; Takemoto DJ. 2009. Loss of protein kinase Cgamma in knockout mice and increased retinal sensitivity to hyperbaric oxygen. Arch Ophthalmol 127(4):500-6. [PubMed: 19365031]  [MGI Ref ID J:151353]

Zeitz KP; Malmberg AB; Gilbert H; Basbaum AI. 2001. Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKC gamma mutant mice. Pain 94(3):245-53. [PubMed: 11731061]  [MGI Ref ID J:103104]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
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 approximately 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 two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	100903 B6129PF2/J	(approximate)
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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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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