Zebrafish DJ-1 is evolutionarily conserved and expressed in dopaminergic neurons

• Published in: Brain research 2006-10, Vol.1113 (1), p.33-44
• Main Authors: Bai, Qing, Mullett, Steven J., Garver, Jessica A., Hinkle, David A., Burton, Edward A.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Blotting, Northern - methods; Blotting, Western - methods; Central nervous system; Chromosomes, Human, Pair 8; Cloning, Molecular - methods; Danio rerio; DJ-1; Dopamine - metabolism; Embryo, Nonmammalian; Evolution, Molecular; Expression pattern; Fundamental and applied biological sciences. Psychology; Gene Expression - physiology; Gene Expression Regulation, Developmental - physiology; Humans; Immunohistochemistry - methods; In Situ Hybridization - methods; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurodegeneration; Neurons - metabolism; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; PARK7; Parkinson's disease; Protein Deglycase DJ-1; Rats; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Sequence Alignment - methods; Transcription start site; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs; Xenopus; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.07.057

Loss-of-function mutations in the human PARK7 gene, encoding DJ-1, are a rare cause of autosomal recessive Parkinson's disease (ARPD). To facilitate generation of a novel vertebrate model, in which to examine the biochemical functions of DJ-1 in vivo, we cloned and characterized the zebrafish orthologue of DJ-1 (zDJ-1). The 0.95 kb zDJ-1 mRNA is expressed in adult zebrafish brain, muscle and gut, and in the embryo from 24 h post-fertilization. The zDJ-1 transcript encodes a 19.8 kDa, 189 amino acid protein, which is 83% identical to human DJ-1. Residues thought to be functionally important sites of post-translational modification in human DJ-1, and critical positions affected by pathogenic missense mutations in ARPD patients, are conserved in zDJ-1. The 14 kb zDJ-1 gene contains six exons and is located on zebrafish chromosome 8; the structure of the gene is highly homologous to human DJ-1, except that there are no alternatively spliced non-coding 5′ exons. The single zDJ-1 first exon shows 5′ end heterogeneity, reflecting multiple transcription start sites. In the adult zebrafish brain, zDJ-1 immunoreactivity was prominent in the cytoplasm of most neurons, and in the neuropil, but was less evident within white matter tracts, consistent with neuronal somatic and dendritic localization. Dopaminergic neurons in each of the major forebrain and diencephalic TH-positive cell groups expressed zDJ-1. These studies show that zDJ-1 is very similar to human DJ-1 and delineate essential resources, allowing further examination of the function and regulation of DJ-1, using the zebrafish as a model.