PUBLICATION
Hypomyelinated vps16 Mutant Zebrafish Exhibit Systemic and Neurodevelopmental Pathologies
- Authors
- Banerjee, S., Bongu, S., Hughes, S.P., Gaboury, E.K., Carver, C.E., Luo, X., Bessert, D.A., Thummel, R.
- ID
- ZDB-PUB-240713-22
- Date
- 2024
- Source
- International Journal of Molecular Sciences 25(13): (Journal)
- Registered Authors
- Luo, Xixia, Thummel, Ryan
- Keywords
- CORVET, HOPS, Vacuolar Protein Sorting 16 (Vps16), behavior, genetic leukoencephalopathy (gLE), memory, mucopolysaccharidosis (MPS), zebrafish
- MeSH Terms
-
- Animals
- Behavior, Animal
- Disease Models, Animal
- Mutation
- Myelin Sheath/metabolism
- Neurodevelopmental Disorders/genetics
- Neurodevelopmental Disorders/metabolism
- Vesicular Transport Proteins*/genetics
- Vesicular Transport Proteins*/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 39000367 Full text @ Int. J. Mol. Sci.
Citation
Banerjee, S., Bongu, S., Hughes, S.P., Gaboury, E.K., Carver, C.E., Luo, X., Bessert, D.A., Thummel, R. (2024) Hypomyelinated vps16 Mutant Zebrafish Exhibit Systemic and Neurodevelopmental Pathologies. International Journal of Molecular Sciences. 25(13):.
Abstract
Homotypic Fusion and Protein Sorting (HOPS) and Class C-core Vacuole/Endosome Tethering (CORVET) complexes regulate the correct fusion of endolysosomal bodies. Mutations in core proteins (VPS11, VPS16, VPS18, and VPS33) have been linked with multiple neurological disorders, including mucopolysaccharidosis (MPS), genetic leukoencephalopathy (gLE), and dystonia. Mutations in human Vacuolar Protein Sorting 16 (VPS16) have been associated with MPS and dystonia. In this study, we generated and characterized a zebrafish vps16(-/-) mutant line using immunohistochemical and behavioral approaches. The loss of Vps16 function caused multiple systemic defects, hypomyelination, and increased neuronal cell death. Behavioral analysis showed a progressive loss of visuomotor response and reduced motor response and habituation to acoustic/tap stimuli in mutants. Finally, using a novel multiple-round acoustic/tap stimuli test, mutants showed intermediate memory deficits. Together, these data demonstrate that zebrafish vps16(-/-) mutants show systemic defects, neurological and motor system pathologies, and cognitive impairment. This is the first study to report behavior abnormalities and memory deficiencies in a zebrafish vps16(-/-) mutant line. Finally, we conclude that the deficits observed in vps16(-/-) zebrafish mutants do not mimic pathologies associated with dystonia, but more align to abnormalities associated with MPS and gLE.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping