PUBLICATION

Abnormal Behavior of Zebrafish Mutant in Dopamine Transporter Is Rescued by Clozapine

Authors
Wang, G., Zhang, G., Li, Z., Fawcett, C.H., Coble, M., Sosa, M.X., Tsai, T., Malesky, K., Thibodeaux, S.J., Zhu, P., Glass, D.J., Fishman, M.C.
ID
ZDB-PUB-190724-18
Date
2019
Source
iScience   17: 325-333 (Journal)
Registered Authors
Fawcett, Caroline, Fishman, Mark C., Wang, Guangliang (Johnny), Zhu, Peixin
Keywords
Behavioral Neuroscience, Biological Sciences, Ethology
MeSH Terms
none
PubMed
31325771 Full text @ iScience
Abstract
Dopamine transporter (SLC6A3) deficiency causes infantile Parkinson disease, for which there is no effective therapy. We have explored the effects of genetically deleting SLC6A3 in zebrafish. Unlike the wild-type, slc6a3-/- fish hover near the tank bottom, with a repetitive digging-like behavior. slc6a3-/- fish manifest pruning and cellular loss of particular tyrosine hydroxylase-immunoreactive neurons in the midbrain. Clozapine, an effective therapeutic for treatment-resistant schizophrenia, rescues the abnormal behavior of slc6a3-/- fish. Clozapine also reverses the abnormalities in the A8 region of the mutant midbrain. By RNA sequencing analysis, clozapine increases the expression of erythropoietin pathway genes. Transgenic over-expression of erythropoietin in neurons of slc6a3-/- fish partially rescues the mutant behavior, suggesting a potential mechanistic basis for clozapine's efficacy.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf3173
    Small Deletion
    zf3174
      Small Deletion
      zf3311TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        slc6a3CRISPR3-slc6a3CRISPR
        slc6a3CRISPR4-slc6a3CRISPR
        1 - 2 of 2
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        Fish
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
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        Mapping
        No data available