Lactational changes in the bone metabolism of mice lacking one copy of the calcitonon receptor gene

Ma, Yue (2012) Lactational changes in the bone metabolism of mice lacking one copy of the calcitonon receptor gene. Masters thesis, Memorial University of Newfoundland.

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    Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
    (Original Version)

Abstract

Calcitonin plays a critical role in preventing excessive bone resorption during lactation. Mice lacking both copies of the calcitonin (CT) gene (CT null mice) lose 55% of bone mineral content (BMC) or twice the amount of wildtype mice during lactation. The calcitonin receptor (CTR) is expressed in the pituitary, lactating breast tissues and bone in mice. However, at which of the three tissues and through which mechanisms the calcitonin acts on CTR to regulate calcium metabolism during reproductive periods are still unclear. This project assesses mice lacking one copy of a CTR gene as a means to understand whether loss of CTR has the same phenotype as the loss of CT during the reproductive cycle. If so, it would enable more studies into the detailed mechanisms of how calcitonin works in each tissue during the reproductive period. -- Wildtype (WT) and heterozygous Ctr gene-deleted sisters (Ctr⁺/⁻) were used to compare BMC changes during pregnancy and lactation using the PixiMus DXA bone densitometer. Ctr null mice cannot be studied because they usually die prior to birth. Urine, serum and milk were collected and analyzed for the mineral content, bone formation, bone resorption markers, and parathyroid hormone (PTH). DXA scanning and urine/serum collections occurred at baseline (before pregnancy), late pregnancy, late lactation, and days 7, 14 and 21 of post-weaning recovery. Tibias were analyzed separately by microcomputed tomography (μCT), the 3-point bend test, and real-time quantitative RT-PCR for Ctr gene expression. -- WT and Ctr⁺/⁻ mice experienced typical lactational changes of BMC and bone microstructure and recovered quickly and fully to baseline levels after weaning. WT and Ctr⁺/⁻ females lost 10.7% ± 3.4% and 10.6% ± 2.0% BMC during lactation relative to baseline level respectively. No significant difference in BMC was observed between WT and Ctr⁺/⁻ mice at any time point. Urine calcium, phosphorus and magnesium levels changed appropriately during reproduction with no significant differences between WT and Ctr⁺/⁻, except for significantly lower urine phosphorus (11.0 ± 2.2 of WT vs. 4.4 ± 1.4 of Ctr⁺/⁻, p < 0.05) and a trend for lower urine calcium and magnesium in Ctr⁺/⁻ at late pregnancy. Bone turnover was increased in both genotypes at late lactation and early recovery. PTH showed an increasing trend from baseline to late lactation. Milk calcium content was the same in both genotypes. Bone strength was significantly decreased at late lactation with no difference between genotypes. WT and Ctr⁺/⁻ had equal levels of Ctr mRNA expression in the tibia. -- In summary, WT and Ctr⁺/⁻ underwent similar changes in bone mass, bone microarchitecture, calciotropic hormones, and serum and urine minerals during pregnancy and lactation. After lactation, the skeleton of each genotype recovered fully and quickly. Loss of one copy of the calcitonin receptor gene does not cause the same phenotype as complete loss of the calcitonin gene (Ctcgrp) likely because one allele transcription of Ctr gene compensates.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/2364
Item ID: 2364
Additional Information: Includes bibliographical references (leaves 95-108).
Department(s): Medicine, Faculty of
Date: 2012
Date Type: Submission
Library of Congress Subject Heading: Calcium--Metabolism--Genetic aspects.; Bone resorption--Treatment.; Lactation.; Calcitonin--Physiological effect.; Calcitonin--Receptors--Physiological effect
Medical Subject Heading: Calcium--Metabolism--Genetic aspects; Bone resorption--Treatment; Lactation; Calcitonin--Physiological effect; Calcitonin--Receptors--Physiological effect

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