RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in Notch4-Induced Mouse Model
Abstract
In year 3, our third investigator continued to repeat the experiments, testing our hypothesis that mouse genetic backgrounds affect the outcome of Rbpj deletion-induced regression of brain arteriovenous malformation (AVM), or BAVM, in the Notch4* mouse model. We had made time-consuming efforts to restore the genetic background of the first investigator and had obtained promising preliminary data to demonstrate the regression seen by the first investigator. We plan to submit the manuscript as soon as we repeat our finding that deletion of Rbpj blocks brain AVM formation. We also re-analyzed the DAPT data and re-designed a new study, with 3 times higher dose but much shorter duration (3 days) DAPT treatment to achieve the goal of testing the efficacies of DAPT in prevention or treatment BAVM formation in the Notch4* mouse model of the disease. We have also completed majority of the ephrin-B2 deletion studies as proposed and as reported in year 2. Our results revealed surprising finding that deleting ephrin-B2 in brain endothelial cells, either arterial or venous endothelial had little effects on brain vascular structure. However, deleting ephrin-B2 in all and venous, but not arterial, endothelium in the whole body leads to chylothorax, illness, and early moribund.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1108208
Entities
People
- Rong Wang
Organizations
- University of California, San Francisco