Rnf-213 Knockout Induces Pericyte Reduction and Blood-Brain Barrier Impairment in Mouse

Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive occlusion of the internal carotid artery and the formation of an abnormal compensatory capillary network at the base of the brain. Genomics studies identified Ring finger protein 213 (RNF213) as a common genetic factor that increases the susceptibility to MMD in East Asian people. However, the function of RNF213 and its roles in pathogenesis of MMD is unclear. Here, we showed that genetic knockout of Rnf213 in mice causes significant pericyte reduction and blood-brain barrier impairment in the cortex. These phenotypes are accompanied with microglia activation and elevated level of proinflammatory cytokines. Additionally, Rnf213-deficient mice showed reduced expression of tight junction proteins, including Occludin, Claudin-5, and ZO-1. Together, these data suggested that RNF213 might contribute to the pathogenesis of MMD through disruption of pericyte homeostasis and blood-brain barrier integrity by dysregulation of inflammatory responses and tight junction formation.

Automated summary

Animal experiments have shown that knockout of the RNF213 gene leads to a reduction in pericytes and impairment of the blood-brain barrier in the cerebral cortex, accompanied by activation of microglia and increased levels of inflammatory cytokines. In addition, Rnf213-deficient mice also showed reduced expression of tight junction proteins. These findings indicate that RNF213 may contribute to the pathogenesis of MMD through disruption of pericyte homeostasis and blood-brain barrier integrity, as well as dysregulation of inflammatory responses and tight junction formation.