Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 Syndrome

ABSTRACT: CTNNB1 syndrome is a rare monogenetic disorder caused by CTNNB1 de novo pathogenic heterozygous loss-of-function variants that result in cognitive and motor disabilities. Treatment is currently lacking; our study addresses this critical need. CTNNB1 encodes β-catenin which is essential for normal brain function via its dual roles in cadherin-based synaptic adhesion complexes and canonical Wnt signal transduction. We have generated a Ctnnb1 germline heterozygous mouse line that displays cognitive and motor deficits, resembling key features of CTNNB1 syndrome in humans. Compared with wildtype littermates, Ctnnb1 heterozygous mice also exhibit decreases in brain β-catenin, β-catenin association with N-cadherin, Wnt target gene expression, and Na/K ATPases, key regulators of changes in ion gr

SUBMITTER: Dr. Jonathan, M Alexander 

PROVIDER: S-SCDT-10_1038-S44321-024-00110-5 | biostudies-other |

REPOSITORIES: biostudies-other