Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism

Steven K. Libutti, Judy S. Crabtree, Dominique Lorang, A. Lee Burns, Chiara Mazzanti, Stephen M. Hewitt, Sarah O'Connor, Jerrold M. Ward, Michael R. Emmert-Buck, Alan Remaley, Marshall Miller, Ewa Turner, H. Richard Alexander, Andrew Arnold, Stephen J. Marx, Francis S. Collins, Allen M. Spiegel

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

The inactivation of the MEN1 tumor suppressor gene in patients leads to a constellation of changes in endocrine tissues, including parathyroid neoplasia, pituitary adenomas, pancreatic neuroendocrine tumors, and carcinoids. To study the pathophysiological consequences of the deletion of the MEN1 gene, we set out to create a mouse model of hyperparathyroidism resulting from the deletion of the Men1 gene in parathyroid tissue. We introduced a Men1 gene flanked by loxP sites into the mouse germ line and then used a parathyroid cell-specific promoter to drive the expression of Cre recombinase, resulting in the deletion of the Men1 gene. Here, we show that loss of Men1 gene function in the parathyroid glands of mice results in histological changes consistent with parathyroid neoplasia as well as systemic hypercalcemia. This model provides a means for dissecting the molecular basis of this familial cancer syndrome and may allow for the development of new strategies to treat related forms of hypercalcemia.

Original languageEnglish (US)
Pages (from-to)8022-8028
Number of pages7
JournalCancer research
Volume63
Issue number22
StatePublished - Nov 15 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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