CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt/cadherin axis.

ABSTRACT: Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder that can cause vision loss. CTNND1 encodes a cellular adhesion protein p120-catenin (p120), which is essential for vascularization with unclear function in postnatal physiological angiogenesis. Here, we applied whole-exome sequencing to 140 probands of FEVR families and identified 3 candidate variants in the human CTNND1 gene. We performed inducible deletion of Ctnnd1 in the postnatal mouse endothelial cells (ECs) and observed typical phenotypes of FEVR with reactive gliosis. Using unbiased proteomics analysis combined with experimental approaches, we conclude that p120 is critical for the integrity of adherens junctions (AJs) and that p120 activates Wnt signaling activity by protecting β-catenin from glycogen synthase ki

SUBMITTER: Yang M 

PROVIDER: S-EPMC9431724 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature