Endocrinology, Vol 135, 2635-2643, Copyright © 1994 by Endocrine Society

ARTICLES

Cloning and characterization of a mouse brain calcitonin receptor complementary deoxyribonucleic acid and mapping of the calcitonin receptor gene

M Yamin, AH Gorn, MR Flannery, NA Jenkins, DJ Gilbert, NG Copeland, DR Tapp, SM Krane and SR Goldring
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston 02114.

We have identified and characterized a mouse brain calcitonin receptor (CTR) complementary DNA (cDNA). This cDNA encodes a receptor protein that, after expression, has high affinity binding for salmon calcitonin (Kd approximately, 12.5 nM) and is coupled to adenylate cyclase. The binding affinity of this expressed receptor for salmon calcitonin is lower than that described for the previously cloned porcine renal and human ovarian CTRs, but is similar to that of the recently described rat brain CTR, designated the C1b form of the receptor. Analysis of the deduced structure of the mouse brain CTR reveals that it is highly related to the other CTR cDNAs that belong to a distinct family of G- protein-coupled receptors with seven transmembrane-spanning domains. The major structural feature that distinguishes the mouse cDNA clone from the other CTRs is the presence of a consecutive 111-basepair nucleotide sequence that encodes a 37-amino acid sequence which is predicted to localize to the first extracellular loop between the second and third transmembrane-spanning domains. We have mapped the CTR gene in the mouse to the proximal region of chromosome 6, which is homologous to the 7q region of human chromosome 7; only a single CTR gene was identified. Preliminary analysis of the mouse CTR gene reveals that it is complex, consisting of multiple exons separated by lengthy introns that would allow for splice variants consistent with the existence of multiple CTR isoforms predicted from the CTR cDNA clones. The differential cellular and tissue distribution of these functionally distinct CTR isoforms provides the molecular basis for the previously reported widespread distribution and functional heterogeneity of the CTR.

This article has been cited by other articles:

				J. Chen and H. S. Randeva Genomic Organization of Mouse Orexin Receptors: Characterization of Two Novel Tissue-Specific Splice Variants Mol. Endocrinol., November 1, 2004; 18(11): 2790 - 2804. [Abstract] [Full Text] [PDF]

				Y. Yaoi, M. Suzuki, H. Tomura, Y. Sasayama, S. Kikuyama, and S. Tanaka Molecular Cloning of Otoconin-22 Complementary Deoxyribonucleic Acid in the Bullfrog Endolymphatic Sac: Effect of Calcitonin on Otoconin-22 Messenger Ribonucleic Acid Levels Endocrinology, August 1, 2003; 144(8): 3287 - 3296. [Abstract] [Full Text] [PDF]

				T. Seck, R. Baron, and W. C. Horne The Alternatively Spliced {Delta}e13 Transcript of the Rabbit Calcitonin Receptor Dimerizes with the C1a Isoform and Inhibits Its Surface Expression J. Biol. Chem., June 13, 2003; 278(25): 23085 - 23093. [Abstract] [Full Text] [PDF]

				D. R. Poyner, P. M. Sexton, I. Marshall, D. M. Smith, R. Quirion, W. Born, R. Muff, J. A. Fischer, and S. M. Foord International Union of Pharmacology. XXXII. The Mammalian Calcitonin Gene-Related Peptides, Adrenomedullin, Amylin, and Calcitonin Receptors Pharmacol. Rev., June 1, 2002; 54(2): 233 - 246. [Abstract] [Full Text] [PDF]

				A. Santhanagopal, P. Chidiac, W. C. Horne, R. Baron, and S. J. Dixon Calcitonin (CT) Rapidly Increases Na+/H+ Exchange and Metabolic Acid Production: Effects Mediated Selectively by the C1a CT Receptor Isoform Endocrinology, October 1, 2001; 142(10): 4401 - 4413. [Abstract] [Full Text] [PDF]

				S. R Goldring The final pathogenetic steps in focal bone erosions in rheumatoid arthritis Ann Rheum Dis, November 1, 2000; 59(90001): i72 - 74. [Full Text] [PDF]

				A. Samura, S. Wada, S. Suda, M. Iitaka, and S. Katayama Calcitonin Receptor Regulation and Responsiveness to Calcitonin in Human Osteoclast-Like Cells Prepared in Vitro using Receptor Activator of Nuclear Factor-{kappa}B Ligand and Macrophage Colony-Stimulating Factor Endocrinology, October 1, 2000; 141(10): 3774 - 3782. [Abstract] [Full Text] [PDF]

				D. Inoue, C. Shih, D. L. Galson, S. R. Goldring, W. C. Horne, and R. Baron Calcitonin-Dependent Down-Regulation of the Mouse C1a Calcitonin Receptor in Cells of the Osteoclast Lineage Involves a Transcriptional Mechanism Endocrinology, March 1, 1999; 140(3): 1060 - 1068. [Abstract] [Full Text]

				D. Inoue, M. Reid, L. Lum, J. Kratzschmar, G. Weskamp, Y. M. Myung, R. Baron, and C. P. Blobel Cloning and Initial Characterization of Mouse Meltrin beta  and Analysis of the Expression of Four MetalloproteaseDisintegrins in Bone Cells J. Biol. Chem., February 13, 1998; 273(7): 4180 - 4187. [Abstract] [Full Text] [PDF]

				J Wang, U. Rout, I. Bagchi, and D. Armant Expression of calcitonin receptors in mouse preimplantation embryos and their function in the regulation of blastocyst differentiation by calcitonin Development, January 11, 1998; 125(21): 4293 - 4302. [Abstract] [PDF]

				G. Pozvek, J. M. Hilton, M. Quiza, S. Houssami, and P. M. Sexton Structure/Function Relationships of Calcitonin Analogues as Agonists, Antagonists, or Inverse Agonists in a Constitutively Activated Receptor Cell System Mol. Pharmacol., April 1, 1997; 51(4): 658 - 665. [Abstract] [Full Text]

				S. Wada, N. Udagawa, T. Akatsu, N. Nagata, T. J. Martin, and D. M. Findlay Regulation by Calcitonin and Glucocorticoids of Calcitonin Receptor Gene Expression in Mouse Osteoclasts Endocrinology, February 1, 1997; 138(2): 521 - 529. [Abstract] [Full Text] [PDF]

				J.-F. Shyu, D. Inoue, R. Baron, and W. C. Horne The Deletion of 14Amino Acids in the Seventh Transmembrane Domain of a Naturally Occurring Calcitonin Receptor Isoform Alters Ligand Binding and Selectively Abolishes Coupling to Phospholipase C J. Biol. Chem., December 6, 1996; 271(49): 31127 - 31134. [Abstract] [Full Text] [PDF]

				O. Anusaksathien, C. Laplace, X. Li, Y. Ren, L. Peng, S. R. Goldring, and D. L. Galson Tissue-specific and Ubiquitous Promoters Direct the Expression of Alternatively Spliced Transcripts from the Calcitonin Receptor Gene J. Biol. Chem., June 15, 2001; 276(25): 22663 - 22674. [Abstract] [Full Text] [PDF]