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Type: Journal article
Title: Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice
Author: Davey, R.
Turner, A.
McManus, J.
Chiu, W.
Tjahyono, F.
Moore, A.
Atkins, G.
Anderson, P.
Ma, C.
Glatt, V.
MacLean, H.
Vincent, C.
Bouxsein, M.
Morris, H.
Findlay, D.
Zajac, J.
Citation: Journal of Bone and Mineral Research, 2008; 23(8):1182-1193
Publisher: Amer Soc Bone & Mineral Res
Issue Date: 2008
ISSN: 0884-0431
Statement of
Rachel A Davey, Andrew G Turner, Julie F McManus, WS Maria Chiu, Francisca Tjahyono, Alison J Moore, Gerald J Atkins, Paul H Anderson, Cathy Ma, Vaida Glatt, Helen E MacLean, Cristina Vincent, Mary Bouxsein, Howard A Morris, David M Findlay, Jeffrey D Zajac
Abstract: It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the Cre/loxP system, in which the CTR is globally deleted by >94% but <100%. Global CTRKOs displayed normal serum ultrafiltrable calcium levels and a mild increase in bone formation in males, showing that the CTR plays a modest physiological role in the regulation of bone and calcium homeostasis in the basal state in mice. Furthermore, the peak in serum total calcium after calcitriol [1,25(OH)2D3]-induced hypercalcemia was substantially greater in global CTRKOs compared with controls. These data provide strong evidence for a biological role of the CTR in regulating calcium homeostasis in states of calcium stress.
Keywords: Femur
Mice, Inbred C57BL
Mice, Knockout
Acid Phosphatase
Receptors, Calcitonin
Gene Targeting
Gene Deletion
Tartrate-Resistant Acid Phosphatase
DOI: 10.1359/JBMR.080310
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