Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism.
Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism.
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发表时间：
2003-11
期刊：
影响因子：
11.2
通讯作者：
S. Libutti;J. Crabtree;D. Lorang;A. Burns;C. Mazzanti;S. Hewitt;Sarah O'Connor;J. Ward;M. Emmert-Buck;A. Remaley;Marshall S. Miller;E. Turner;H. Alexander;A. Arnold;S. Marx;F. Collins;A. Spiegel
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作者：
S. Libutti;J. Crabtree;D. Lorang;A. Burns;C. Mazzanti;S. Hewitt;Sarah O'Connor;J. Ward;M. Emmert-Buck;A. Remaley;Marshall S. Miller;E. Turner;H. Alexander;A. Arnold;S. Marx;F. Collins;A. Spiegel
MEN1肿瘤抑制基因的失活导致内分泌组织的一系列变化，包括甲状旁腺肿瘤、垂体腺瘤、胰腺神经内分泌肿瘤和类癌。为了研究MEN1基因缺失的病理生理学后果，我们开始创建甲状旁腺组织中MEN1基因缺失导致的甲状旁腺功能亢进症的小鼠模型。我们将带有loxP位点的MEN1基因导入小鼠胚系，然后用甲状旁腺细胞特异性启动子驱动Cre重组酶的表达，导致MEN1基因缺失。在这里，我们展示了MEN1基因在小鼠甲状旁腺中功能的丧失导致与甲状旁腺肿瘤和全身性高钙血症相一致的组织学变化。这一模型提供了一种剖析这种家族性癌症综合征的分子基础的方法，并可能允许开发治疗相关形式的高钙血症的新策略。
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.