Intricate MIB1-NOTCH-GATA6 Interactions in Cardiac Valvular and Septal Development.

ABSTRACT: Genome-wide association studies and experimental mouse models implicate the MIB1 and GATA6 genes in congenital heart disease (CHD). Their close physical proximity and conserved synteny suggest that these two genes might be involved in analogous cardiac developmental processes. Heterozygous Gata6 loss-of-function mutations alone or humanized Mib1 mutations in a NOTCH1-sensitized genetic background cause bicuspid aortic valve (BAV) and a membranous ventricular septal defect (VSD), consistent with MIB1 and NOTCH1 functioning in the same pathway. To determine if MIB1-NOTCH and GATA6 interact in valvular and septal development, we generated compound heterozygote mice carrying different Mib1 missense (Mib1^K735R and Mib1^V943F)

SUBMITTER: Pineiro-Sabaris R 

PROVIDER: S-EPMC11277162 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature