Loss-of-function mutations in the CTNNB1 gene cause β-catenin deficiency, leading to CTNNB1 syndrome, a rare neurodevelopmental disorder marked by motor and cognitive impairments. Because the disease stems from single-allele mutations that vary widely, a broadly applicable corrective strategy is needed. Since CTNNB1 is dosage-sensitive, therapies must preserve normal regulation, and in some cases may also need to suppress harmful mutant transcripts.

CTNNB1 syndrome is a neurodevelopmental disorder characterized by intellectual disability, global developmental delay, microcephaly and motor disabilities, among others, caused by pathogenic loss-of-function variants in the CTNNB1 gene, which encodes β-catenin. This syndrome has no treatment option, with only supportive care available. To address this unmet medical need, researchers from the Broad Institute and Tufts University School of Biomedical Sciences have developed a Ctnnb1 germline heterozygote murine model that mimics the human CTNNB1 syndrome.