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A shifted repertoire of endocannabinoid genes in the zebrafish (Danio rerio)

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Abstract

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.

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Acknowledgments

This work was partially supported by an unrestricted grant from GW Pharmaceuticals, Salisbury, Wiltshire SP4 0JQ, UK. The authors thank Ken Mackie and Alistair Nunn for helpful discussions. Conflict of Interest Statement: none of the authors had any financial or personal relationships that influenced the work submitted.

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Authors and Affiliations

  1. GW Pharmaceuticals, 53 Washington Street Ext., Middlebury, VT, 05753, USA

    J. M. McPartland

  2. Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand

    Michelle Glass

  3. Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078, Pozzuoli (Napoli), Italy

    Isabel Matias

  4. Department of Biology, University of Vermont, Room 120A Marsh Life Science Building, Burlington, VT, 05405, USA

    Ryan W. Norris & C. William Kilpatrick

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  1. J. M. McPartland
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  2. Michelle Glass
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  5. C. William Kilpatrick
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Correspondence to J. M. McPartland.

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Communicated by T. Becker.

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McPartland, J.M., Glass, M., Matias, I. et al. A shifted repertoire of endocannabinoid genes in the zebrafish (Danio rerio). Mol Genet Genomics 277, 555–570 (2007). https://doi.org/10.1007/s00438-007-0207-3

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  • DOI: https://doi.org/10.1007/s00438-007-0207-3

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