In-depth characterization of the CaV2.2-knockout mouse line

Abstract

Abstract The voltage-gated calcium channel Ca V 2.2 is predominantly located in neuronal synapses, where it plays a role in pain signaling and neurotransmitter release. Furthermore, Ca V 2.2 is important during early central nervous system development, as it is subsequently replaced by other calcium channels. A number of mouse lines with disrupted Ca V 2.2 channels have been developed through the utilization of a gene-targeting vector. The Ca V 2.2-deficient mice primarily exhibited reduced anxiety-linked behavior and response to pain stimuli. In a previous study, we observed hyperactivity and seizures in Ca V 2.2-knockout mice. Given the absence of prior descriptions of these characteristics, an in-depth characterization was conducted. This characterization included longitudinal behavioral studies, as well as histological, proteomic, and metabolomic analyses. Irrespective of the frequency with which testing was conducted, a variety of behaviors were observed (e.g., hyperactivity and increased exploratory behavior) in comparison with wild-type mice. The frequency and severity of the performed tests demonstrated a positive correlation with the magnitude of the difference in molecular markers between Ca V 2.2-knockout and wild-type mice. Seizures were observed but were not common. These results suggest that the Ca V 2.2-knockout mouse lines are susceptible to repeated stress stimuli during experimental studies. The mice are characterized by hyperactivity, explorative behavior, and sometimes experience seizures.