JAX Mouse Strain Datasheet - 005855

B6.Cg-Tg(Camk2a-Prkaca)426Tabe/J

Stock No:: 005855 |; R(AB)

Cryo Recovery

Overview

Also Known As: R(AB)

These R(AB) mice express a transgene containing the cAMP-dependent protein kinase A (PKA or PRKACA) RI alpha regulatory subunit, R(AB) and exhibit a reduction of hippocampal PKA activity with a significant decrease in the late phase of long-term potentiation in the hippocampus.

Donating Investigator

Ted Abel, University of Pennsylvania

Genetic overview

Genetic Background	Generation

Tg(Camk2a-Prkaca)426Tabe

Allele Type
Transgenic (Inserted expressed sequence)

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed 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.

Expression Data

Expressed Gene	Prkaca, protein kinase, cAMP dependent, catalytic, alpha, mouse, laboratory
Site of Expression

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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: J:38837

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Genetics

Tg(Camk2a-Prkaca)426Tabe

Allele Symbol: Tg(Camk2a-Prkaca)426Tabe

Allele Name	transgene insertion 426, Ted Abel
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	CaMKII-R(AB); R(AB); R(AB)-2
Gene Symbol and Name	Tg(Camk2a-Prkaca)426Tabe, transgene insertion 426, Ted Abel
Gene Synonym(s)	CaMKII-R(AB); R(AB); R(AB)-2
Promoter	Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Expressed Gene	Prkaca, protein kinase, cAMP dependent, catalytic, alpha, mouse, laboratory
Strain of Origin	(C57BL/6J x CBA/J)F2
Chromosome	UN
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.
Mutations Made By	Ted Abel, University of Pennsylvania

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Alzheimer's Disease
- Behavioral and Learning Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg(Camk2a-Prkaca)426Tabe/0
involves: C57BL/6J * CBA/J

homeostasis/metabolism phenotype

abnormal enzyme/coenzyme activity
- 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
- mutants have normal short term memory in tests but long term memory is severely defective compared to wild-type
- similar results are obtained when control mice are treated with the PKA inhibitor Rp-cAMPs prior to training
- 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 impairedsponses 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

abnormal spatial learning
- 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
- transgenic mice show decreased ethanol preference and consumption compared to wild-type

impaired righting response
- mice are more sensitive to ethanol-induced sedation than wild-type

nervous system phenotype

reduced long term potentiation
- there is a defect in Schaffer collateral L-LTP
- 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 mutantsPSP slopes - 123%, 199% and 176% at 20, 60 and 180 minutes); early-LTP induced by one or two stimuli is unchanged in mutants

References

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: J:38837

Additional - 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: 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: 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: 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: 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: 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: 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: 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: 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: J:108069

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The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 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.

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Also Known As: R(AB)

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Camk2a-Prkaca)426Tabe

Allele Symbol: Tg(Camk2a-Prkaca)426Tabe

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Camk2a-Prkaca)426Tabe/0involves: C57BL/6J * CBA/J

homeostasis/metabolism phenotype

behavior/neurological phenotype

nervous system phenotype

References

Additional - Tg(Camk2a-Prkaca)426Tabe related

Genotyping Protocols

Breeding Considerations

Mating System

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Camk2a-Prkaca)426Tabe/0
involves: C57BL/6J * CBA/J