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 language | English (US) |
|---|---|
| Pages (from-to) | 8022-8028 |
| Number of pages | 7 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 22 |
| State | Published - Nov 15 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism
AU - Libutti, Steven K.
AU - Crabtree, Judy S.
AU - Lorang, Dominique
AU - Burns, A. Lee
AU - Mazzanti, Chiara
AU - Hewitt, Stephen M.
AU - O'Connor, Sarah
AU - Ward, Jerrold M.
AU - Emmert-Buck, Michael R.
AU - Remaley, Alan
AU - Miller, Marshall
AU - Turner, Ewa
AU - Alexander, H. Richard
AU - Arnold, Andrew
AU - Marx, Stephen J.
AU - Collins, Francis S.
AU - Spiegel, Allen M.
PY - 2003/11/15
Y1 - 2003/11/15
N2 - 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.
AB - 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.
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M3 - Article
VL - 63
SP - 8022
EP - 8028
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 22
ER -