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Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice.

Publication ,  Journal Article
Balenga, N; Koh, J; Azimzadeh, P; Hogue, J; Gabr, M; Stains, JP; Olson, JA
Published in: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
May 2019

The relationship between impaired calcium sensing, dysregulated parathyroid hormone (PTH) secretion, and parathyroid cell proliferation in parathyroid neoplasia is not understood. We previously reported that a GTPase activating protein, regulator of G-protein signaling 5 (RGS5) is overexpressed in a subset of parathyroid tumors associated with primary hyperparathyroidism (PHPT) and that RGS5 can inhibit signaling from the calcium-sensing receptor (CASR). In vivo, we found that RGS5-null mice have abnormally low PTH levels. To gain a better understanding of the potential role of RGS5 overexpression in parathyroid neoplasia and PHPT and to investigate whether inhibition of CASR signaling can lead to parathyroid neoplasia, we created and characterized a transgenic mouse strain overexpressing RGS5 specifically in the parathyroid gland. These mice develop hyperparathyroidism, bone changes reflective of elevated PTH, and parathyroid neoplasia. Further, expression of exogenous RGS5 in normal human parathyroid cells results in impaired signaling from CASR and negative feedback on PTH secretion. These results provide evidence that RGS5 can modulate signaling from CASR and support a role for RGS5 in the pathogenesis of PHPT through inhibition of CASR signaling. © 2019 American Society for Bone and Mineral Research.

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Published In

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

DOI

EISSN

1523-4681

ISSN

0884-0431

Publication Date

May 2019

Volume

34

Issue

5

Start / End Page

955 / 963

Related Subject Headings

  • Signal Transduction
  • Receptors, Calcium-Sensing
  • RGS Proteins
  • Mice, Transgenic
  • Mice
  • Hyperparathyroidism
  • Gene Expression Regulation
  • Animals
  • Anatomy & Morphology
  • 32 Biomedical and clinical sciences
 

Citation

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Balenga, N., Koh, J., Azimzadeh, P., Hogue, J., Gabr, M., Stains, J. P., & Olson, J. A. (2019). Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice. Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research, 34(5), 955–963. https://doi.org/10.1002/jbmr.3674
Balenga, Nariman, James Koh, Pedram Azimzadeh, Joyce Hogue, Mostafa Gabr, Joseph P. Stains, and John A. Olson. “Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice.Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research 34, no. 5 (May 2019): 955–63. https://doi.org/10.1002/jbmr.3674.
Balenga N, Koh J, Azimzadeh P, Hogue J, Gabr M, Stains JP, et al. Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2019 May;34(5):955–63.
Balenga, Nariman, et al. “Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice.Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research, vol. 34, no. 5, May 2019, pp. 955–63. Epmc, doi:10.1002/jbmr.3674.
Balenga N, Koh J, Azimzadeh P, Hogue J, Gabr M, Stains JP, Olson JA. Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2019 May;34(5):955–963.
Journal cover image

Published In

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

DOI

EISSN

1523-4681

ISSN

0884-0431

Publication Date

May 2019

Volume

34

Issue

5

Start / End Page

955 / 963

Related Subject Headings

  • Signal Transduction
  • Receptors, Calcium-Sensing
  • RGS Proteins
  • Mice, Transgenic
  • Mice
  • Hyperparathyroidism
  • Gene Expression Regulation
  • Animals
  • Anatomy & Morphology
  • 32 Biomedical and clinical sciences