Establishing a Mouse Model for Brain Arteriovenous Malformations
This project aims to establish and characterize a novel mouse model for hereditary hemorrhagic telangiectasia (HHT). HHT is an autosomal dominant disorder known to be caused by mutations in the receptor activin receptor-like kinase (ALK1). Arteriovenous malformations (AVMs) are a hallmark of HHT, and brain AVMs (bAVMs) can be particularly risky as they can cause hemorrhagic stroke. HHT-bAVM formation mechanism is not well understood and there are no preventions or treatments. Animal models of Alk1 deficiency can facilitate the study of HHT-bAVM pathogenesis; however, existing HHT-Alk1 mouse models are limited in their ability to recapitulate clinical bAVM features. Thus, I propose to establish a superior HHT-bAVM mouse model, with genetics and symptoms closer to clinical HHT-bAVM and having high bAVM penetrance, as well as characterize the cellular parameters accompanying HHT-bAVM pathogenesis in these mice to better understand HHT-bAVM progression mechanism. Successfully completing this project will provide a crucial system and valuable insights into HHT pathogenesis and facilitate therapeutic development.
Message to Sponsor
- Major: Molecular & Cell Biology, Nutritional Sciences
- Sponsor: Pergo Fund
- Mentor: Sai Yuan, Rong Wang