Complementary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome.

Wac deletion mutants in mice and zebrafish display craniofacial, behavioral, and neurological phenotypes similar to DeSanto-Shinawi Syndrome, highlighting their relevance as models.

• Why it matters: Understanding the molecular mechanisms behind neurodevelopmental symptoms like autism and seizures in DESSH is limited due to a lack of vertebrate models, hindering progress in targeted research and therapies.
• What they did: Researchers created Wac/wac deletion mutants in mice and zebrafish, analyzing craniofacial features, behavior, GABAergic neuron impacts, seizure susceptibility, brain volume differences, and transcriptional changes.
• The result: The models replicate key DESSH features, providing valuable tools for future molecular studies and advancing understanding of Wac’s role in neurodevelopmental disorders.