A shifted repertoire of endocannabinoid genes in the zebrafish (Danio rerio)
Mol Genet Genomics. 2007-01-26; 277(5): 555-570
DOI: 10.1007/s00438-007-0207-3
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1. Mol Genet Genomics. 2007 May;277(5):555-70. doi: 10.1007/s00438-007-0207-3.
Epub 2007 Jan 26.
A shifted repertoire of endocannabinoid genes in the zebrafish (Danio rerio).
McPartland JM(1), Glass M, Matias I, Norris RW, Kilpatrick CW.
Author information:
(1)GW Pharmaceuticals, Middlebury, VT 05753, USA.
The zebrafish has served as a model organism for developmental biology.
Sequencing its genome has expanded zebrafish research into physiology and
drug-development testing. Several cannabinoid pharmaceuticals are in
development, but expression of endocannabinoid receptors and enzymes remains
unknown in this species. We conducted a bioinformatics analysis of the zebrafish
genome using 17 human endocannabinoid genes as a reference set. Putative
zebrafish orthologs were identified in filtered BLAST searches as reciprocal
best hits. Orthology was confirmed by three in silico methods: phylogenetic
testing, synteny analysis, and functional mapping. Zebrafish expressed orthologs
of cannabinoid receptor 1, transient receptor potential channel vanilloid
receptor 4, GPR55 receptor, fatty acid amide hydrolase 1, monoacylglycerol
lipase, NAPE-selective phospholipase D, abhydrolase domain-containing protein 4,
and diacylglycerol lipase alpha and beta; and paired paralogs of cannabinoid
receptor 2, fatty acid amide hydrolase 2, peroxisome proliferator-activated
receptor alpha, prostaglandin-endoperoxide synthase 2, and transient receptor
potential cation channel subtype A1. Functional mapping suggested the orthologs
of transient receptor potential vanilloid receptor 1 and peroxisome
proliferator-activated receptor gamma lack specific amino acids critical for
cannabinoid ligand binding. No orthologs of N-acylethanolamine acid amidase or
protein tyrosine phosphatase, non-receptor type 22 were identified. In
conclusion, the zebrafish genome expresses a shifted repertoire of
endocannabinoid genes. In vitro analyses are warranted before using zebrafish
for cannabinoid development testing.
DOI: 10.1007/s00438-007-0207-3
PMID: 17256142 [Indexed for MEDLINE]