Hypomyelinated vps16 Mutant Zebrafish Exhibit Systemic and Neurodevelopmental Pathologies

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 mucopolysacchar...

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Published in:	International journal of molecular sciences Vol. 25; no. 13; p. 7260
Main Authors:	Banerjee, Shreya, Bongu, Shivani, Hughes, Sydney P, Gaboury, Emma K, Carver, Chelsea E, Luo, Xixia, Bessert, Denise A, Thummel, Ryan
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-07-2024
Subjects:	Animals Apoptosis behavior Behavior, Animal Cell cycle Disease Models, Animal Dystonia genetic leukoencephalopathy (gLE) memory mucopolysaccharidosis (MPS) Mutation Myelin Sheath - metabolism Neurodevelopmental Disorders - genetics Neurodevelopmental Disorders - metabolism Pathology Photoreceptors Proteins Siblings Vacuolar Protein Sorting 16 (Vps16) Vesicular Transport Proteins - genetics Vesicular Transport Proteins - metabolism Zebrafish Zebrafish - genetics Zebrafish Proteins - genetics Zebrafish Proteins - metabolism Vacuolar Protein Sorting 16 (Vps16) memory genetic leukoencephalopathy (gLE) CORVET HOPS zebrafish behavior mucopolysaccharidosis (MPS)
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Summary:	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 have been associated with MPS and dystonia. In this study, we generated and characterized a zebrafish 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 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 mutant line. Finally, we conclude that the deficits observed in zebrafish mutants do not mimic pathologies associated with dystonia, but more align to abnormalities associated with MPS and gLE.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms25137260