Yasuhara Jun, Aljuhani Mona, Choudhury Talita Z, Rao Anupama, Conroy Sara, Ueyama Yukie, LaHaye Stephanie, Schultz Karlee, Cameron Emily M, Manivannan Sathiya N, Majumdar Uddalak, Garg Vidu
Center for Cardiovascular Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; The Heart Center, Nationwide Children's Hospital, Columbus, Ohio, USA.
Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
JACC Basic Transl Sci. 2025 Jul 31;10(9):101354. doi: 10.1016/j.jacbts.2025.101354.
Here, we describe Notch1;Gata5 compound mutant mice as a novel mouse model of highly penetrant congenital aortic valve disease displaying bicuspid aortic valve and progressive aortic valve stenosis. Further, we find downregulation of smooth muscle genes in the neonatal aortic valves in Notch1;Gata5 compound mice consistent with an immature valve phenotype. Our findings demonstrate a novel genetic interaction between Notch1 and Gata5 in mice that is critical for proper aortic valve development. This novel model is an important tool to define dysregulated signaling pathways for congenital aortic valve stenosis and stenotic disease progression that can be investigated as therapeutic targets.
在此，我们将Notch1;Gata5复合突变小鼠描述为一种新型的高 penetrant先天性主动脉瓣疾病小鼠模型，该模型表现出二叶式主动脉瓣和进行性主动脉瓣狭窄。此外，我们发现Notch1;Gata5复合小鼠新生主动脉瓣中平滑肌基因下调，这与未成熟瓣膜表型一致。我们的研究结果表明，Notch1和Gata5在小鼠中存在一种新型的遗传相互作用，这对主动脉瓣的正常发育至关重要。这个新型模型是定义先天性主动脉瓣狭窄和狭窄性疾病进展中失调信号通路的重要工具，这些信号通路可作为治疗靶点进行研究。
