Motility phenotype in a zebrafish vmat2 mutant.
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...
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0259753&type=printable |
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| author | Hildur Sóley Sveinsdóttir Amanda Decker Christian Christensen Pablo Botella Lucena Haraldur Þorsteinsson Elena Richert Valerie Helene Maier Robert Cornell Karl Ægir Karlsson |
| author_facet | Hildur Sóley Sveinsdóttir Amanda Decker Christian Christensen Pablo Botella Lucena Haraldur Þorsteinsson Elena Richert Valerie Helene Maier Robert Cornell Karl Ægir Karlsson |
| author_sort | Hildur Sóley Sveinsdóttir |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cef2d16ff3db43e0967934d3285f8c45 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-cef2d16ff3db43e0967934d3285f8c452025-08-20T03:16:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01171e025975310.1371/journal.pone.0259753Motility phenotype in a zebrafish vmat2 mutant.Hildur Sóley SveinsdóttirAmanda DeckerChristian ChristensenPablo Botella LucenaHaraldur ÞorsteinssonElena RichertValerie Helene MaierRobert CornellKarl Ægir KarlssonIn 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0259753&type=printable |
| spellingShingle | Hildur Sóley Sveinsdóttir Amanda Decker Christian Christensen Pablo Botella Lucena Haraldur Þorsteinsson Elena Richert Valerie Helene Maier Robert Cornell Karl Ægir Karlsson Motility phenotype in a zebrafish vmat2 mutant. PLoS ONE |
| title | Motility phenotype in a zebrafish vmat2 mutant. |
| title_full | Motility phenotype in a zebrafish vmat2 mutant. |
| title_fullStr | Motility phenotype in a zebrafish vmat2 mutant. |
| title_full_unstemmed | Motility phenotype in a zebrafish vmat2 mutant. |
| title_short | Motility phenotype in a zebrafish vmat2 mutant. |
| title_sort | motility phenotype in a zebrafish vmat2 mutant |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0259753&type=printable |
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