CRISPR/CasRx suppresses KRAS-induced brain arteriovenous malformation developed in postnatal brain endothelial cells in mice.

ABSTRACT: Brain arteriovenous malformations (bAVMs) are anomalies forming vascular tangles connecting the arteries and veins, which cause hemorrhagic stroke in young adults. Current surgical approaches are highly invasive, and alternative therapeutic methods are warranted. Recent genetic studies identified KRAS mutations in endothelial cells of bAVMs; however, the underlying process leading to malformation in the postnatal stage remains unknown. Here we established a mouse model of bAVM developing during the early postnatal stage. Among 4 methods tested, mutant KRAS specifically introduced in brain endothelial cells by brain endothelial cell-directed adeno-associated virus (AAV) and endothelial cell-specific Cdh5-CreERT2 mice successfully induced bAVMs in the postnatal period. Mutant KRAS led to the

SUBMITTER: Saito S 

PROVIDER: S-EPMC11601911 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature