RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in Notch4 Induced Mouse Model
Technical Report,30 Sep 2016,29 Sep 2017
University of California, San Francisco San Francisco United States
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We started deleting Rbpj in our P16 mutant mice already developed arteriovenous malformation AVM then monitored and analyzed the mice with and without deletion, along with controls at moribund states. We show that endothelial deletion of Rbpj reduced and slowed arteriovenous malformation disease progression, as it doubled the length of time for mutant mice to reach moribundity. We obtained data and performed statistical analysis, showing in all assays for AVM hallmarks, endothelial deletion of Rbpj reduced the severity in these evaluation, which includes whole mount frontal cortex from brain with FITC-lectin endothelial cells to highlight vessels diameters of mutant AV connections AV shunting using microsphere passage assay AVM nidus vessels using MICROFIL casting assay brain hemorrhage and regions of hypoxia by HypoxyprobeTM immunostaining. Our data suggest that deleting Rbpj can induce AVM regression in our mouse model. We are preparing a manuscript to report this finding.
- Medicine and Medical Research