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Published on: May 4, 2015
Rnf-213 Knockout Induces Pericyte Reduction and Blood-Brain Barrier Impairment in Mouse
Wei Li1, Xingyang Niu1, Yuanyuan Dai2
1Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Abstract:
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.
Insights
Ring finger protein 213 (RNF213) deficiency in mice disrupts blood-brain barrier integrity, causing pericyte loss and inflammation. This suggests RNF213 is crucial for maintaining brain vascular health and may play a role in Moyamoya disease pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Vascular Biology
Background:
- Moyamoya disease (MMD) is a rare cerebrovascular disorder.
- The Ring finger protein 213 (RNF213) gene is a known susceptibility factor for MMD, particularly in East Asian populations.
- The precise function of RNF213 in MMD pathogenesis remains largely unknown.
Purpose of the Study:
- To investigate the role of RNF213 in the pathogenesis of Moyamoya disease.
- To elucidate the cellular and molecular mechanisms underlying RNF213's function in the brain.
Main Methods:
- Genetic knockout of Rnf213 in a mouse model.
- Assessment of pericyte number and blood-brain barrier integrity.
- Analysis of microglia activation and pro-inflammatory cytokine levels.
- Evaluation of tight junction protein expression.
Main Results:
- Rnf213 knockout mice exhibited significant pericyte reduction and blood-brain barrier impairment.
- These mice showed increased microglia activation and elevated pro-inflammatory cytokines.
- Expression of tight junction proteins (Occludin, Claudin-5, ZO-1) was reduced in Rnf213-deficient mice.
Conclusions:
- RNF213 plays a critical role in maintaining pericyte homeostasis and blood-brain barrier integrity.
- Dysregulation of RNF213 may contribute to MMD pathogenesis by affecting inflammatory responses and tight junction formation.
- These findings provide new insights into the molecular mechanisms of Moyamoya disease.
