Open AccessMotility phenotype in a zebrafish vmat2 mutant
Author(s) -
Hildur Sóley Sveinsdóttir,
Amanda R. Decker-Farrell,
Christian Christensen,
Pablo Botella Lucena,
Haraldur Þorsteinsson,
Elena Richert,
Valerie H. Maier,
Robert A. Cornell,
Karl Karlsson
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259753
Subject(s) - mutant , biology , monoamine neurotransmitter , zebrafish , glial cell line derived neurotrophic factor , dopamine , wild type , phenotype , microbiology and biotechnology , motility , neurotrophic factors , neuroscience , genetics , serotonin , gene , receptor
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.