Molecular and behavioral effects of a null mutation in all PKA C beta isoforms.
The cAMP-dependent protein kinase (PKA) Cbeta gene encodes three isoforms, two of which (Cbeta2 and Cbeta3) are transcribed from neural-specific promoters. Here we report the effects of knocking out all PKA Cbeta subunit isoforms in mice. Total PKA activity was unaffected in the hippocampus and amygdala, while basal PKA activity was reduced by 26% in the brains of Cbetaall(-/-) mice despite a compensatory increase in Calpha protein. Cued fear conditioning was disrupted in Cbetaall(-/-) mice when tested on a mixed C57BL/6/129 background but was indistinguishable from wild type mice when bred onto a 98% C57BL/6 background. This suggests an amygdala-specific deficit in the Cbetaall null mice that is sensitive to strain-specific genetic modifiers. Behavioral testing including locomotor activity, contextual fear conditioning, and conditioned taste aversion was normal in Cbetaall null mice on the 50% C57BL/6J background. We conclude that Cbeta protein is not essential for neuronal development or function but may play a more subtle role in memory that is modulated by strain-specific genetic modifiers.
Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Douglas G
DG
Howe
Jesse C
JC
Wiley
G Stanley
GS
McKnight
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000201:enzymology; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics* / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D017353:Gene Deletion; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D021122:Protein Subunits; D013649:Taste / Q000235:genetics / Q000502:physiology
D007527:Isoenzymes; D021122:Protein Subunits; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; D017868:Cyclic AMP-Dependent Protein Kinases; C463959:protein kinase A Calpha