ZFIN ID: ZDB-PUB-190724-18
Abnormal Behavior of Zebrafish Mutant in Dopamine Transporter Is Rescued by Clozapine
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.
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
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.