Standardization of A Physiologic Hypoparathyroidism Animal Model

PLoS One. 2016 Oct 3;11(10):e0163911. doi: 10.1371/journal.pone.0163911. eCollection 2016.

Abstract

Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.

MeSH terms

  • Animals
  • Biomarkers
  • Body Weight
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Calcium / blood
  • Calcium / urine
  • Diet / adverse effects
  • Disease Models, Animal
  • Hypoparathyroidism / blood*
  • Hypoparathyroidism / diagnosis
  • Hypoparathyroidism / etiology
  • Hypoparathyroidism / physiopathology*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Parathyroid Hormone / blood
  • Parathyroidectomy
  • Phosphorus / blood
  • Phosphorus / urine
  • Rats
  • X-Ray Microtomography

Substances

  • Biomarkers
  • Parathyroid Hormone
  • Phosphorus
  • Calcium

Grants and funding

This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C-1557-010015, URL: https://www.khidi.or.kr) and by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2015R1D1A1A09058485, URL: http://www.nrf.re.kr/) Grant receiver: HSK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.