Somatic gene transfer in the development of an animal model for primary hyperparathyroidism

James M. Wilson, Mariann Grossman, Anne R. Thompson, Cindy Lupassikis, Andrew Rosenberg, John T. Potts, Henry M. Kronenberg, Richard C. Mulligan, Samuel R. Nussbaum

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6 Scopus citations

Abstract

The overproduction of hormones is associated with a variety of endocrinological disorders. We have used somatic cell gene transfer of human PTH (hPTH) to develop an animal model of hypercalcemia and osteoclastic skeletal resorption. Recombinant retroviruses were used to transduce a functional hPTH gene into cultured rat fibroblasts. The recombinant-derived preproparathyroid hormone peptide was appropriately processed in this ectopic cell, and intact hPTH (1-84) was secreted at a high level (2-5 ng/106 cells/24 h). Transplantation of the PTH-secreting cells into syngeneic rat recipients was associated with the development of hypercalcemia mediated by increasing serum concentrations of hPTH. Thyroparathyroidectomy in these hypercalcemic rats producing hPTH did not result in hypocalcemia and tetany, which was observed in control animals undergoing thyroparathyroidectomy. Chronic overproduction of hPTH (60 days) was associated with severe hypercalcemia, metastatic calcification, and histological changes of osteoclastic resorption of bone. This animal model will be useful in studying the pathophysiology of severe hyperparathyroidism in humans and should help in the evaluation of new medical therapies for hypercalcemia.

Original languageEnglish
Pages (from-to)2947-2954
Number of pages8
JournalEndocrinology
Volume130
Issue number5
StatePublished - May 1 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Wilson, J. M., Grossman, M., Thompson, A. R., Lupassikis, C., Rosenberg, A., Potts, J. T., Kronenberg, H. M., Mulligan, R. C., & Nussbaum, S. R. (1992). Somatic gene transfer in the development of an animal model for primary hyperparathyroidism. Endocrinology, 130(5), 2947-2954.