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Animal models of hyperfunctioning parathyroid diseases for drug development

Yasuo Imanishi1, Masaaki Inaba, Takehisa Kawata

  • 1Osaka City University Graduate School of Medicine, Metabolism, Endocrinology and Molecular Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545 8585, Japan +81 6 6645 3806 ; +81 6 6645 3808 ; imanishi@med.osaka-cu.ac.jp.

Expert Opinion on Drug Discovery
|March 16, 2013
PubMed
Abstract

Insights

New transgenic mice models with parathyroid-targeted cyclin D1 overexpression show promise for studying hyperparathyroidism in chronic kidney disease (CKD). These models mimic human disease progression, aiding the development of novel therapeutics for CKD-mineral and bone disorders.

Area of Science:

  • Endocrinology
  • Nephrology
  • Oncology

Background:

  • Mineral and bone disorders are linked to high mortality in chronic kidney disease (CKD) patients.
  • Hyperphosphatemia, vitamin D metabolism disorders, and secondary hyperparathyroidism of uremia (SHPT) are key therapeutic targets in CKD.
  • Current animal models, like uremic rats, have limitations in lifespan and SHPT severity.

Purpose of the Study:

  • To review the molecular pathogenesis of hyperfunctioning parathyroid diseases.
  • To discuss the application of animal models in developing new therapeutics for hyperparathyroidism.

Main Methods:

  • Utilized PTH-cyclin D1 transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene.
  • Observed parathyroid cell proliferation, biochemical hyperparathyroidism, and bone abnormalities.
  • Assessed age-dependent development of hyperparathyroidism and parathyroid cell hyperplasia.

Main Results:

  • Transgenic mice developed abnormal parathyroid cell proliferation and biochemical hyperparathyroidism with bone abnormalities.
  • The mice exhibited age-dependent hyperparathyroidism, suitable for precise drug testing.
  • Parathyroid cell hyperplasia and monoclonal expansion, mirroring refractory SHPT in patients, were observed.

Conclusions:

  • PTH-cyclin D1 transgenic mice represent a valuable model for studying hyperparathyroidism.
  • This model aids in the development of new therapeutics for CKD-related bone and mineral disorders.
  • The model's characteristics closely resemble human refractory SHPT, enhancing its clinical relevance.

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