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
(all 12)
PubMed
39000367 Full text @ Int. J. Mol. Sci.
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
Marker Marker Type Name
vps16GENEVPS16 core subunit of CORVET and HOPS complexes
1 - 1 of 1
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Figures
Figure Gallery (9 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
vps16wsu4/wsu4 (AB)controlDay 5
vps16wsu4/wsu4 (AB)controlDays 7-13
vps16wsu4/wsu4 (AB)standard conditionsDay 4
vps16wsu4/wsu4 (AB)standard conditionsDay 5
vps16wsu4/wsu4 (AB)standard conditionsDay 6
vps16wsu4/wsu4 (AB)standard conditionsDays 7-13
vps16wsu4/wsu4 (AB)standard conditionsDays 7-13
vps16wsu4/wsu4 (AB)standard conditionsDays 7-13
vps16wsu4/wsu4 (AB)standard conditionsDays 7-13
vps16wsu4/wsu4 (AB)standard conditionsDays 7-13
1 - 10 of 32
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
wsu4
    		Complex
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    vps16CRISPR2-vps16CRISPR
    1 - 1 of 1
    Show
    Fish
    Fish
    AB
    vps16wsu4/wsu4 (AB)
    1 - 2 of 2
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    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    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):.