| First Author | Klomp A | Year | 2022 |
| Journal | PLoS One | Volume | 17 |
| Issue | 3 | Pages | e0263197 |
| PubMed ID | 35353835 | Mgi Jnum | J:322894 |
| Mgi Id | MGI:7259476 | Doi | 10.1371/journal.pone.0263197 |
| Citation | Klomp A, et al. (2022) The voltage-gated Ca2+ channel subunit alpha2delta-4 regulates locomotor behavior and sensorimotor gating in mice. PLoS One 17(3):e0263197 |
| abstractText | Voltage-gated Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the alpha2delta-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. alpha2delta-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of alpha2delta-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of alpha2delta-4 knockout (KO) mice. alpha2delta-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas alpha2delta-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor coordination in the rotarod assay. alpha2delta-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for alpha2delta-4 in sensorimotor gating and motor function and identify alpha2delta-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants. |
