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 journalArticle

70 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Parathyroid Glands
Hyperparathyroidism
Gene Deletion
Multiple Endocrine Neoplasia Type 1
Hypercalcemia
Genes
Neoplasms
Neuroendocrine Tumors
Carcinoid Tumor
Pituitary Neoplasms
Tumor Suppressor Genes
Germ Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Libutti, S. K., Crabtree, J. S., Lorang, D., Burns, A. L., Mazzanti, C., Hewitt, S. M., ... Spiegel, A. M. (2003). Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism. Cancer Research, 63(22), 8022-8028.

Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism. / Libutti, Steven K.; Crabtree, Judy S.; Lorang, Dominique; Burns, A. Lee; Mazzanti, Chiara; Hewitt, Stephen M.; O'Connor, Sarah; Ward, Jerrold M.; Emmert-Buck, Michael R.; Remaley, Alan; Miller, Marshall; Turner, Ewa; Alexander, H. Richard; Arnold, Andrew; Marx, Stephen J.; Collins, Francis S.; Spiegel, Allen M.

In: Cancer Research, Vol. 63, No. 22, 15.11.2003, p. 8022-8028.

Research output: Contribution to journalArticle

Libutti, SK, Crabtree, JS, Lorang, D, Burns, AL, Mazzanti, C, Hewitt, SM, O'Connor, S, Ward, JM, Emmert-Buck, MR, Remaley, A, Miller, M, Turner, E, Alexander, HR, Arnold, A, Marx, SJ, Collins, FS & Spiegel, AM 2003, 'Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism', Cancer Research, vol. 63, no. 22, pp. 8022-8028.
Libutti SK, Crabtree JS, Lorang D, Burns AL, Mazzanti C, Hewitt SM et al. Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism. Cancer Research. 2003 Nov 15;63(22):8022-8028.
Libutti, Steven K. ; Crabtree, Judy S. ; Lorang, Dominique ; Burns, A. Lee ; Mazzanti, Chiara ; Hewitt, Stephen M. ; O'Connor, Sarah ; Ward, Jerrold M. ; Emmert-Buck, Michael R. ; Remaley, Alan ; Miller, Marshall ; Turner, Ewa ; Alexander, H. Richard ; Arnold, Andrew ; Marx, Stephen J. ; Collins, Francis S. ; Spiegel, Allen M. / Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism. In: Cancer Research. 2003 ; Vol. 63, No. 22. pp. 8022-8028.
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