VRK2 deficiency elicits aggressive behavior in female zebrafish

Vaccinia-related kinase 2 (VRK2) VRK2 is one of the serine/threonine kinases that was originally identified in highly proliferative cells such as thymocytes and fetal liver cells. GWAS studies were reported that VRK2 was related molecule with neuropsychiatric diseases. And in vitro studies reported that VRK2 plays an important role in cell division and cell cycle regulation. However, little is known about the molecular mechanism and physiological function of VRK2 on the central nervous systems in vivo. In this study, we established vrk2 deficient (VRK2 KO) zebrafish and found that VRK2 KO body size and brain size were not change compare with their control zebrafish (WT). And we performed a series of behavior tests such as a novel tank diving test, mirror test, and social preference test. In the behavior, we observed that the aggressive behavior was significantly enhanced in female VRK2 KO on the mirror test, and abnormal behavior was observed in the social preference test. Additionally, we measured neurotransmitter to investigate mechanism of these malbehavior, VRK2 KO female zebrafish showed low gamma-aminobutyric acid (GABA) content in the brain. GABA related to neuronal dendrites and spines pruning. Therefore, we analyzed the formation of neuronal dendrites and spines in the forebrain area using Golgi staining. We found a high density of neuronal dendrites in VRK2KO female zebrafish when compared with WT. These results suggest that VRK2 is a tight relationship with alteration of the morphology of nerve dendrites in the forebrain. That cause the malbehavior on female zebrafish.