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

Stock number: 005855
Product name: R(AB)
Research areas: Neurobiology Research

Description

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.

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.

Allele

Symbol: Tg(Camk2a-Prkaca)426Tabe
Name: transgene insertion 426, Ted Abel
MGI accession ID: MGI:3626071
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Camk2a-Prkaca)426Tabe
Marker name: transgene insertion 426, Ted Abel
Chromosome: UN
Strain of origin: (C57BL/6J x CBA/J)F2
Expressed genes: Prkaca,protein kinase, cAMP dependent, catalytic, 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.