ABSTRACT
The teleost fish has been widely used in creating neurodegenerative models. Here we describe the teleost medaka fish Parkinson's disease (PD) models we developed using toxin treatment and genetic engineering. 1-Methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors and tunicamycin treatment in our model fish replicated some salient features of PD: selective dopamine cell loss and reduced spontaneous movement with the last three toxins producing inclusion bodies ubiquitously in the brain. Despite the ubiquitous distribution of the inclusion bodies, the middle diencephalic dopaminergic neurons were particularly vulnerable to these toxins, supporting the idea that this dopamine cluster is similar to the human substantia nigra. PTEN-induced putative kinase 1 (PINK1) homozygous mutants also showed reduced spontaneous swimming movements. These data indicate that medaka fish can serve as a new model animal of PD. In this review we summarize our previous data and discuss future prospects.
Subject(s)
Animals , Humans , Brain , Dopamine , Dopaminergic Neurons , Genetic Engineering , Inclusion Bodies , Lysosomes , Oryzias , Oxidopamine , Parkinson Disease , Phosphotransferases , Proteasome Inhibitors , Protein Kinases , Substantia Nigra , Swimming , TunicamycinABSTRACT
Ciliary neurotrophic factor (CNTF) is one of the important factors in neuronal survival. Mutation in CNTF gene was found first in Japanese. We analyzed the CNTF genotype of 187 healthy volunteer of Korean, and compared the frequency difference in CNTF gene mutation among Korean, Japanese, and other nations or race. The number of normal homozygote was 138 (73.8%), mutant homozygote 47 (25.1%), and mutant homozygote was 2 (1.1%). The mutated allele frequency of CNTF gene in Korean was 13.6%, which was not significantly different from that of other nations or race (10~20%).