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.
