Complementary vertebrate <i>Wac</i> models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome
Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments and neurobehavioral phenotypes, including autism and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by…
DeSanto-Shinawi Syndrome (DESSH) is a rare disorder caused by pathogenic variants in the WAC gene. It results in neurodevelopmental changes that cause cognitive impairments and neurobehavioral phenotypes, such as autism, seizures, and developmental delay. While limited studies exist, no vertebrate models have been developed to understand these changes.
Researchers have now created both murine and zebrafish Wac/wac deletion mutants to determine if their phenotypes mirror those observed in individuals with DESHH syndrome. Both mutant models exhibit craniofacial and behavioral changes similar to those found in DESHH. Additionally, impacts on GABAergic neurons and seizures susceptibility were observed in both models.
Mice also showed differences in brain volumes between sexes and relevant behaviors. The study uncovered transcriptional impacts of Wac loss-of-function in mice, paving the way for future molecular studies into DESHH syndrome and further elucidating the biology of Wac.
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