PUBLICATION
Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish
- Authors
- Grone, B.P., Marchese, M., Hamling, K.R., Kumar, M.G., Krasniak, C.S., Sicca, F., Santorelli, F.M., Patel, M., Baraban, S.C.
- ID
- ZDB-PUB-160311-4
- Date
- 2016
- Source
- PLoS One 11: e0151148 (Journal)
- Registered Authors
- Baraban, Scott, Grone, Brian
- Keywords
- Zebrafish, Larvae, Heart rate, Epilepsy, Embryos, Behavior, Biological locomotion, Phenotypes
- MeSH Terms
-
- Animals
- Behavior, Animal*
- Disease Models, Animal
- Epilepsy*/genetics
- Epilepsy*/metabolism
- Humans
- Munc18 Proteins*/genetics
- Munc18 Proteins*/metabolism
- Mutation*
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 26963117 Full text @ PLoS One
Citation
Grone, B.P., Marchese, M., Hamling, K.R., Kumar, M.G., Krasniak, C.S., Sicca, F., Santorelli, F.M., Patel, M., Baraban, S.C. (2016) Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish. PLoS One. 11:e0151148.
Abstract
Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b) have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing "dark-flash" visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping