title: Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice.
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)(2)D(3)]-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.
authors.affiliation: Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. r.davey@unimelb.edu.au
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Davey
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Turner
authors.forename: Julie F
authors.initials: JF
authors.lastname: McManus
authors.forename: W S Maria
authors.initials: WS
authors.lastname: Chiu
authors.forename: Francisca
authors.initials: F
authors.lastname: Tjahyono
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Moore
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Atkins
authors.forename: Paul H
authors.initials: PH
authors.lastname: Anderson
authors.forename: Cathy
authors.initials: C
authors.lastname: Ma
authors.forename: Vaida
authors.initials: V
authors.lastname: Glatt
authors.forename: Helen E
authors.initials: HE
authors.lastname: MacLean
authors.forename: Cristina
authors.initials: C
authors.lastname: Vincent
authors.forename: Mary
authors.initials: M
authors.lastname: Bouxsein
authors.forename: Howard A
authors.initials: HA
authors.lastname: Morris
authors.forename: David M
authors.initials: DM
authors.lastname: Findlay
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002116:Calcitonin / Q000097:blood; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000473:pathology; D017353:Gene Deletion; D018390:Gene Targeting; D006934:Hypercalcemia / Q000378:metabolism / Q000517:prevention & control*; D019426:Integrases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D018003:Receptors, Calcitonin / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D000199:Actins; D007527:Isoenzymes; D018003:Receptors, Calcitonin; D002116:Calcitonin; C045073:Cre recombinase; D019426:Integrases; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol; D002118:Calcium