Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Hemizygote         (Female x Male)   03-SEP-08 Species laboratory mouse Generation N11p   Donating Investigator Ted Abel,   University of Pennsylvania

Description
Mice hemizygous for the transgene are viable and fertile with no gross anatomical abnormalities or structural lesions within the hippocampus or other regions. Transgene expression is observed in hippocampus (CA1, CA3, and dentate gyrus), neocortex, olfactory bulb, striatum, and amygdala. Transgenic mice have a 50% reduction in basal cAMP-dependent protein kinase A (PKA or PRKACA) activity, defective protein synthesis-dependent late phase of long-term potentiation, and reduced place cell stability in hippocampus. Mice have defective long-term, but not short-term, memory in hippocampus-based spatial and non-spatial tasks. This parallels the phenotype observed in mice treated with inhibitors of PKA or inhibitors of protein synthesis. Functional magnetic resonance imaging reveals reduced CA1 hippocampal signal. Transgenic mice are more sensitive to ethanol-induced sedation. Mice expressing this transgene may be useful in a wide variety of memory studies, including Alzheimer's disease, hippocampus-dependent long term memory, protein synthesis-dependent memory, amnesia, or age-related memory decline.

Development
The cAMP-dependent protein kinase A (PKA or PRKACA) RIalpha regulatory subunit, R(AB), was mutated at both cAMP binding sites and placed under control of the mouse Camk2a promoter. The resulting construct was injected into the pronuclei of (B6CBAF1/J x B6CBAF1/J) zygotes. Chimeric males (founder line 426, R(AB)-2) were bred to C57BL/6J females. At some point, hemizygotes were bred to B6CBAF1/J to rescue the line. After the rescue, hemizygotes were bred to C57BL/6J for more than 10 generations before arrival at The Jackson Laboratory.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Camk2a

002362	B6.129P2-Camk2atm1Sva/J
007574	B6.Cg-Tg(Camk2a-Crebbp*)1364Tabe/J
005359	B6.Cg-Tg(Camk2a-cre)T29-1Stl/J
007004	B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ
003010	B6;CBA-Tg(Camk2a-tTA)1Mmay/J
004995	C3H-Tg(Camk2a-Creb1/ESR1)3Sva/J
006575	C57BL/6-Camk2atm1Vyb/J
006579	C57BL/6-Tg(Camk2a-Bdnf)A9Stl/J
005087	C57BL/6-Tg(Camk2a-IDE)1Selk/J
005086	C57BL/6-Tg(Camk2a-MME)3Selk/J
008833	C57BL/6-Tg(Camk2a-UBB)3413-1Fwvl/J

View Strains carrying other alleles of Camk2a     (11 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

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.

Tg(Camk2a-Prkaca)426Tabe/0

        involves: C57BL/6J * CBA/J

• homeostasis/metabolism phenotype
• abnormal enzyme/coenzyme activity (MGI Ref ID J:38837)
  • in transgenics, basal PKA activity in hippocampal extracts (239 pmol/min/mg) is 50% of wild-type (499 pmol/min/mg); when kinase is activated with 5 um cAMP, activity is attenuated by 25% with respect to wild-type mice.
• behavior/neurological phenotype
• abnormal contextual conditioning behavior (MGI Ref ID J:38837)
  • mutants have normal short term memory in tests but long term memory is severely defective compared to wild-type
  • training mice with a single conditioned stimulus (CS)/ unconditioned stimulus (US) pairing and testing mice 1, 3, 6, and 24 hours after training shows similar responses in transgenic and control mice at 1 hour, but dramatic reduction in contextual fear responses relative to wild-type at 3, 6, and 24 hours post-training; this indicates short term memory is normal in mutants, but long term memory is impaired
  • similar results are obtained when control mice are treated with the PKA inhibitor Rp-cAMPs prior to training
• abnormal spatial learning (MGI Ref ID J:38837)
  • in a probe trial of the Morris water maze test, mutants search less selectively and spend less time in the target quadrant than control mice, but mutants do not have reduced visual acuity or motor coordination
• decreased alcohol consumption (MGI Ref ID J:70175)
  • transgenic mice show decreased ethanol preference and consumption compared to wild-type
• impaired righting response (MGI Ref ID J:70175)
  • mice are more sensitive to ethanol-induced sedation than wild-type
• nervous system phenotype
• reduced long term potentiation (MGI Ref ID J:38837)
  • when four 100 Hz trains are applied to hippocampal slices from mutant mice, it elicits a continually decaying potentiation (fEPSP slopes - 202%, 144% and 107% at 20, 60 and 180 minutes); in wild-type this stimulation induces robust, long-lasting L-LTP (fEPSP slopes - 123%, 199% and 176% at 20, 60 and 180 minutes); early-LTP induced by one or two stimuli is unchanged in mutants
  • there is a defect in Schaffer collateral L-LTP

View Research Applications

Research Applications

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

Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(Camk2a-Prkaca)426Tabe
Allele Name		transgene insertion 426, Ted Abel
Allele Type		Transgenic (random, expressed)
Common Name(s)		CaMKII-R(AB); R(AB); R(AB)-2;
Mutation Made By		Ted Abel,   University of Pennsylvania
Strain of Origin		(C57BL/6J x CBA/J)F2
Expressed Gene		Prkaca, protein kinase, cAMP dependent, catalytic, alpha, mouse, laboratory
Promoter		Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Molecular Note		The cAMP-dependent protein kinase A (PKA or PRKACA) RIalpha regulatory subunit, R(AB), was mutated at both cAMP binding sites and placed under control of the mouse Camk2a promoter. [MGI Ref ID J:38837]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Camk2a-Prkaca)426Tabe, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Abel T; Nguyen PV; Barad M; Deuel TA; Kandel ER; Bourtchouladze R. 1997. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 88(5):615-26. [PubMed: 9054501]  [MGI Ref ID J:38837]

Additional References

Tg(Camk2a-Prkaca)426Tabe related

Bourtchouladze R; Abel T; Berman N; Gordon R; Lapidus K; Kandel ER. 1998. Different training procedures recruit either one or two critical periods for contextual memory consolidation, each of which requires protein synthesis and PKA. Learn Mem 5(4-5):365-74. [PubMed: 10454361]  [MGI Ref ID J:110284]

Gould TJ; Bizily SP; Tokarczyk J; Kelly MP; Siegel SJ; Kanes SJ; Abel T. 2004. Sensorimotor gating deficits in transgenic mice expressing a constitutively active form of Gs alpha. Neuropsychopharmacology 29(3):494-501. [PubMed: 14694347]  [MGI Ref ID J:134103]

Isiegas C; Park A; Kandel ER; Abel T; Lattal KM. 2006. Transgenic inhibition of neuronal protein kinase A activity facilitates fear extinction. J Neurosci 26(49):12700-7. [PubMed: 17151273]  [MGI Ref ID J:116707]

Kelly MP; Isiegas C; Cheung YF; Tokarczyk J; Yang X; Esposito MF; Rapoport DA; Fabian SA; Siegel SJ; Wand G; Houslay MD; Kanes SJ; Abel T. 2007. Constitutive activation of Galphas within forebrain neurons causes deficits in sensorimotor gating because of PKA-dependent decreases in cAMP. Neuropsychopharmacology 32(3):577-88. [PubMed: 16738544]  [MGI Ref ID J:134123]

Rotenberg A; Abel T; Hawkins RD; Kandel ER; Muller RU. 2000. Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity J Neurosci 20(21):8096-102. [PubMed: 11050131]  [MGI Ref ID J:65203]

Small SA; Wu EX; Bartsch D; Perera GM; Lacefield CO; DeLaPaz R; Mayeux R; Stern Y; Kandel ER. 2000. Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice. Neuron 28(3):653-64. [PubMed: 11163257]  [MGI Ref ID J:111960]

Wand G; Levine M; Zweifel L; Schwindinger W; Abel T. 2001. The cAMP-protein kinase A signal transduction pathway modulates ethanol consumption and sedative effects of ethanol. J Neurosci 21(14):5297-303. [PubMed: 11438605]  [MGI Ref ID J:70175]

Woo NH; Duffy SN; Abel T; Nguyen PV. 2000. Genetic and pharmacological demonstration of differential recruitment of cAMP-dependent protein kinases by synaptic activity. J Neurophysiol 84(6):2739-45. [PubMed: 11110804]  [MGI Ref ID J:130699]

Young JZ; Isiegas C; Abel T; Nguyen PV. 2006. Metaplasticity of the late-phase of long-term potentiation: a critical role for protein kinase A in synaptic tagging. Eur J Neurosci 23(7):1784-94. [PubMed: 16623835]  [MGI Ref ID J:108069]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygotes are bred to wildtype siblings or to inbred C57BL/6J mice.
Mating System	+/+ sibling x Hemizygote         (Female x Male)   03-SEP-08

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). 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
	Noncarrier
	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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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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