PUBLICATION
Restoring Shank3 in the rostral brainstem of shank3ab-/- zebrafish autism models rescues sensory deficits
- Authors
- Kozol, R.A., James, D.M., Varela, I., Sumathipala, S.H., Züchner, S., Dallman, J.E.
- ID
- ZDB-PUB-211221-18
- Date
- 2021
- Source
- Communications biology 4: 1411 (Journal)
- Registered Authors
- Dallman, Julia, James, David, Sumathipala, Sureni
- Keywords
- none
- MeSH Terms
-
- Animals
- Autistic Disorder/genetics*
- Autistic Disorder/physiopathology
- Brain Stem/physiology*
- Chromosome Deletion
- Chromosome Disorders/genetics*
- Chromosome Disorders/metabolism
- Chromosomes, Human, Pair 22/genetics
- Chromosomes, Human, Pair 22/metabolism
- Disease Models, Animal
- Mutation
- Nerve Tissue Proteins/genetics*
- Nerve Tissue Proteins/metabolism
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 34921227 Full text @ Commun Biol
Citation
Kozol, R.A., James, D.M., Varela, I., Sumathipala, S.H., Züchner, S., Dallman, J.E. (2021) Restoring Shank3 in the rostral brainstem of shank3ab-/- zebrafish autism models rescues sensory deficits. Communications biology. 4:1411.
Abstract
People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly exhibit reduced responses to sensory stimuli; yet the changes in brain-wide activity that link these symptoms to mutations in the shank3 gene remain unknown. Here we quantify movement in response to sudden darkness in larvae of two shank3 zebrafish mutant models and show that both models exhibit dampened responses to this stimulus. Using brain-wide activity mapping, we find that shank3-/- light-sensing brain regions show normal levels of activity while sensorimotor integration and motor regions are less active. Specifically restoring Shank3 function in a sensorimotor nucleus of the rostral brainstem enables the shank3-/- model to respond like wild-type. In sum, we find that reduced sensory responsiveness in shank3-/- models is associated with reduced activity in sensory processing brain regions and can be rescued by restoring Shank3 function in the rostral brainstem. These studies highlight the importance of Shank3 function in the rostral brainstem for integrating sensory inputs to generate behavioral adaptations to changing sensory stimuli.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping