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Journal of Biochemistry Advance Access published online on June 16, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn084
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© 2008 The Japanese Biochemical Society

Genomic and Expression Analysis of Canine Calcitonin Receptor-Stimulating Peptides and Calcitonin/Calcitonin Gene-Related Peptide

Tsukasa Osaki, Takeshi Katafuchi and Naoto Minamino*

Department of Pharmacology, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan

*Address correspondence to: Dr. Naoto Minamino, PhD, Department of Pharmacology, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. Phone: +81-6-6833-5012 (ext. 2507), Fax: +81-6-6835-5349, E-mail: minamino{at}ri.ncvc.go.jp

Received May 13, 2008; Accepted June 9, 2008


  Abstract

Summary

Calcitonin receptor-stimulating peptides (CRSPs) are new members of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified in pigs, dogs and other domestic animals, and CRSP-1 is an active ligand for the CT receptor (CT-R). We recently sequenced porcine CRSP genes (Crsps) and found similarity with the CT/CGRP gene (Ct/Cgrp) in sequence and genomic organization. In this study, we identified five Crsps, Crsp-1 to Crsp-5, in dogs. Crsp-1 has five exons with an exon-intron organization identical to that of porcine Crsp-1 or Crsp-2, while Crsp-2 and Crsp-3 have additional CT-2- and CT-3-coding exons like Ct/Cgrp. Crsp-2 was renamed as Ct-2/Crsp-2 because both CRSP-2 and CT-2 mRNAs were tissue-specifically expressed. Crsp-4 and Crsp-5 are presumably generated by retrotransposition. We postulate that Crsps were generated from the gene duplication of Ct/Cgrp, and gained their diversity during mammalian evolution. Among the canine CTs and CRSPs, CRSP-1, CT-1 and CT-2 are active ligands for the CT-R, but CRSP-2 and others are inactive. Canine CRSP-1 and CT-2 are expressed in the central and peripheral systems, while CT-1 is localized in the thyroid gland. These findings indicate that dogs can be used for an experimental model as analyzing the physiological roles of the CT/CGRP/CRSP family.

Key Words: calcitonin receptor-stimulating peptide, calcitonin, calcitonin gene-related peptide, calcitonin receptor, genomic organization


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