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Title: | Motility phenotype in a zebrafish vmat2 mutant | Authors: | Sveinsdottir, Hildur Soley Decker , Amanda Christensen, Christian BOTELLA LUCENA, Pablo Porsteinsson, Haraldur Richert, Elena Maier, Valerie Helene Cornell, Robert Karlsson, Karl Aegir |
Editors: | Neuhauss, Stephan C.F. | Issue Date: | 2022 | Publisher: | PUBLIC LIBRARY SCIENCE | Source: | PLoS One, 17 (1) (Art N° e0259753) | Abstract: | 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. | Notes: | Karlsson, KÆ (corresponding author), 3Z, Reykjavik, Iceland.; Karlsson, KÆ (corresponding author), Reykjavik Univ, Sch Sci & Engn, Reykjavik, Iceland.; Karlsson, KÆ (corresponding author), Univ Iceland, Biomed Ctr, Reykjavik, Iceland. karlsson@ru.is |
Keywords: | Animals;Brain;Dopamine;Dopamine Plasma Membrane Transport Proteins;Glial Cell Line-Derived Neurotrophic Factor;Locomotion;Vesicular Monoamine Transport Proteins;Zebrafish;Zebrafish Proteins | Document URI: | http://hdl.handle.net/1942/37038 | ISSN: | 1932-6203 | e-ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0259753 | ISI #: | WOS:000765956200005 | Rights: | 2022 Sveinsdo´ttir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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Motility phenotype in a zebrafish vmat2 mutant.pdf | Published version | 1.89 MB | Adobe PDF | View/Open |
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