Parathyroid-specific double knockout of Gq and G11 α-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+-sensing receptor

Nina Wettschureck, EunAh Lee, Steven K. Libutti, Stefan Offermanns, Pamela G. Robey, Allen M. Spiegel

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Germline knockout of the extracellular Ca2+-sensing receptor (CaR) leads to a phenotype that includes severe hypercalcemia, hyperparathyroidism, relative hypocalciuria, skeletal abnormalities, retarded growth, and early postnatal death. To investigate the role of heterotrimeric G proteins in CaR signaling, we used cre/lox technology to delete the respective α-subunits of Gq and G11 selectively in parathyroid cells. Mice that were PTH-Cre+/-; Gnaqflox/flox; Gna11-/- (PTH-Gαq/Gα11-double knockouts) were viable, but showed all the features of germline knockout of the CaR except hypocalcuria. Our results demonstrate the critical role of both Gq and G11 in mediating inhibition of PTH secretion by extracellular Ca2+.

Original languageEnglish (US)
Pages (from-to)274-280
Number of pages7
JournalMolecular Endocrinology
Volume21
Issue number1
DOIs
StatePublished - Jan 2007

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Calcium-Sensing Receptors
Phenotype
Heterotrimeric GTP-Binding Proteins
Hyperparathyroidism
Hypercalcemia
Technology
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Parathyroid-specific double knockout of Gq and G11 α-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+-sensing receptor. / Wettschureck, Nina; Lee, EunAh; Libutti, Steven K.; Offermanns, Stefan; Robey, Pamela G.; Spiegel, Allen M.

In: Molecular Endocrinology, Vol. 21, No. 1, 01.2007, p. 274-280.

Research output: Contribution to journalArticle

Wettschureck, Nina ; Lee, EunAh ; Libutti, Steven K. ; Offermanns, Stefan ; Robey, Pamela G. ; Spiegel, Allen M. / Parathyroid-specific double knockout of Gq and G11 α-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+-sensing receptor. In: Molecular Endocrinology. 2007 ; Vol. 21, No. 1. pp. 274-280.
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