title: Cloning and expression analysis of a Parkinson's disease gene, uch-L1, and its promoter in zebrafish.
abstract: Three genes, alpha-synuclein, parkin, and ubiquitin C-terminal hydrolase L1 (UCH-L1), have been associated with inherited forms of Parkinson's disease (PD), although their in vivo functions have remained largely unknown. To develop an animal model for the molecular study of PD, we cloned zebrafish uch-L1 cDNA and its gene promoter. Sequence analysis revealed that the zebrafish Uch-L1 is highly homologous (79%) to the human UCH-L1, which is a member of the deubiquitinating enzymes. By whole-mount in situ hybridization, we examined the spatiotemporal expression of uch-L1 mRNA in developing zebrafish embryos. The uch-L1 mRNAs are detected in neuronal cells at the first day of embryo development. The expression domain of uch-L1 overlaps with that of tyrosine hydroxylase, a molecular marker for dopaminergic neurons, in the ventral diencephalon, an equivalent structure to the substantia nigra where PD progresses in human. To further analyze the tissue-specific regulation of uch-L1 gene expression, we also tested its gene promoter activity and showed a preferential neuronal expression in transient transgenic zebrafish embryos. These results suggest that uch-L1 may have an important role in the development of neuronal cells in early embryos as well as in the degeneration and disease of neuronal cells in late adult brain.
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Ok-Lye
authors.initials: OL
authors.lastname: Son
authors.forename: Hyun-Taek
authors.initials: HT
authors.lastname: Kim
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Ji
authors.forename: Kyeong-Won
authors.initials: KW
authors.lastname: Yoo
authors.forename: Myungchull
authors.initials: M
authors.lastname: Rhee
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017385:Sequence Homology; D013045:Species Specificity; D014018:Tissue Distribution; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; C482067:uchl1 protein, zebrafish; D043222:Ubiquitin Thiolesterase