title: Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism.
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.
authors: Surgery Branch, Center for Cancer Research, National Cancer Institute/NIH, 10 Center Drive, Room 2B07, Bethesda, MD 20892, USA. Steven_Libutti@nih.gov
authors: Steven K
authors: SK
authors: Libutti
authors: Judy S
authors: JS
authors: Crabtree
authors: Dominique
authors: D
authors: Lorang
authors: A Lee
authors: AL
authors: Burns
authors: Chiara
authors: C
authors: Mazzanti
authors: Stephen M
authors: SM
authors: Hewitt
authors: Sarah
authors: S
authors: O'Connor
authors: Jerrold M
authors: JM
authors: Ward
authors: Michael R
authors: MR
authors: Emmert-Buck
authors: Alan
authors: A
authors: Remaley
authors: Marshall
authors: M
authors: Miller
authors: Ewa
authors: E
authors: Turner
authors: H Richard
authors: HR
authors: Alexander
authors: Andrew
authors: A
authors: Arnold
authors: Stephen J
authors: SJ
authors: Marx
authors: Francis S
authors: FS
authors: Collins
authors: Allen M
authors: AM
authors: Spiegel
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D003433:Crosses, Genetic; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000235:genetics*; D006961:Hyperparathyroidism / Q000097:blood / Q000235:genetics*; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010282:Parathyroid Neoplasms / Q000097:blood / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D002118:Calcium