Restoring Shank3 in the rostral brainstem of shank3ab-/- zebrafish autism models rescues sensory deficits

ABSTRACT: People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly present with symptoms of sensory hyporeactivity. To investigate how shank3 mutations impact brain circuits and contribute to sensory hyporeactivity, we generated two shank3 zebrafish mutant models. These shank3 mutants exhibit hyporeactivity to visual stimuli. Using whole-brain activity mapping, we show that light receptive brain nuclei show normal levels of activity while sensorimotor integration and motor regions are less active in shank3-/- mutants. Specifically rescuing Shank3 in a sensorimotor nucleus of the rostral brainstem is sufficient to rescue shank3-/- mutant hyporeactivity. In summary, reduced sensory responsiveness in shank3-/- mutant is associated with reduced activity across the brain an

ORGANISM(S): Danio rerio (zebrafish)

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PROVIDER: S-BSST741 | biostudies-other |

REPOSITORIES: biostudies-other