Motility phenotype in a zebrafish vmat2 mutant.

Autor: Sveinsdóttir HS; 3Z, Reykjavik, Iceland., Decker A; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, United States of America., Christensen C; 3Z, Reykjavik, Iceland., Lucena PB; School of Science and Engineering, Reykjavik University, Reykjavik, Iceland., Þorsteinsson H; 3Z, Reykjavik, Iceland., Richert E; School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.; Department of Psychology, University of Oldenburg, Oldenburg, Germany., Maier VH; Biomedical Center, University of Iceland, Reykjavik, Iceland., Cornell R; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, United States of America., Karlsson KÆ; 3Z, Reykjavik, Iceland.; School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.; Biomedical Center, University of Iceland, Reykjavik, Iceland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Jan 05; Vol. 17 (1), pp. e0259753. Date of Electronic Publication: 2022 Jan 05 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0259753
Abstrakt: In the present study, we characterize a novel zebrafish mutant of solute carrier 18A2 (slc18a2), also known as vesicular monoamine transporter 2 (vmat2), that exhibits a behavioural phenotype partially consistent with human Parkinson´s disease. At six days-post-fertilization, behaviour was analysed and demonstrated that vmat2 homozygous mutant larvae, relative to wild types, show changes in motility in a photomotor assay, altered sleep parameters, and reduced dopamine cell number. Following an abrupt lights-off stimulus mutant larvae initiate larger movements but subsequently inhibit them to a lesser extent in comparison to wild-type larvae. Conversely, during a lights-on period, the mutant larvae are hypomotile. Thigmotaxis, a preference to avoid the centre of a behavioural arena, was increased in homozygotes over heterozygotes and wild types, as was daytime sleep ratio. Furthermore, incubating mutant larvae in pramipexole or L-Dopa partially rescued the motor phenotypes, as did injecting glial cell-derived neurotrophic factor (GDNF) into their brains. This novel vmat2 model represents a tool for high throughput pharmaceutical screens for novel therapeutics, in particular those that increase monoamine transport, and for studies of the function of monoamine transporters.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KÆK and HÞ are co-founders and shareholders in 3Z. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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