REGULATION OF MINERAL METABOLISM

矿物质代谢的调节

• 批准号: 3876374
• 负责人: S J MARX
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3876374
• 关键词: adenoma; autosomal dominant trait; calcium disorder; child (0-11); chromosome disorders; endocrine neoplasm; histocompatibility gene; homozygote; hormone regulation /control mechanism; human subject; human tissue; hypercalcemia; hyperparathyroidism; kidney metabolism; linkage mapping; mitogens; molecular cloning; molecular oncology; multiple endocrine neoplasia; neoplasm /cancer genetics; pancreatic islet disorder; parathyroid disorder; pituitary disorders; pituitary neoplasms; tissue /cell culture; tumor suppressor genes

Disorders of mineral metabolism have been evaluated with methods extending from epidemiology to cellular and molecular biology. Two forms of familial hyperparathyroidism have been characterized in detail. Familial hypocalciuric hypercalcemia is an autosomal dominant trait associated with abnormal interactions with calcium in parathyroid and kidney. Familial multiple endocrine neoplasia type 1 (EMEN1) is an autosomal dominant trait causing hyperfunction of parathyroids, pancreatic iseit and anterior pituitary. It is associated with gradual but abnormal proliferation of the tissues affected. Genetic linkage studies in a large kindred have localized the MEN1 gene to the long arm of chromosome 11. Plasma from affected persons shows high mitogenic activity in plasma may contribute to primary hyperparathyroidism in EMEN1. Analysis of blood and parathyroid tumor DNA has revealed that EMEN1 parathyroids often show clonal loss of alleles in the region of the EMEN1 gene on chromosome 11. Thus the EMEN1 gene functions as a tumor suppressor gene, analogous to the retinoblastoma gene. Analysis of sporadic parathyroid adenomas revealed that 25% showed allelic loss in a similar region. Thus the clonal inactivation of the EMEN1 gene may also be a contributing factor in many sporadic parathyroid adenomas.

矿物质代谢紊乱的评估方法， 从流行病学到细胞和分子生物学。 两种家庭形式 甲状旁腺功能亢进症已经被详细描述。 家族性 低尿钙高钙血症是一种常染色体显性特征， 与甲状旁腺和肾脏中钙的异常相互作用。 家族性 多发性内分泌肿瘤1型（EMEN1）是一种常染色体显性遗传性状 引起甲状旁腺功能亢进，胰腺炎和前 脑垂体 它与逐渐但不正常的增殖有关， 受影响的组织。 在一个大家族中进行的遗传连锁研究 将MEN1基因定位于11号染色体的长臂。 血浆 受影响的人在血浆中显示高促有丝分裂活性可能有助于 原发性甲状旁腺功能亢进EMEN1。 血液和甲状旁腺分析 肿瘤DNA显示，EMEN1甲状旁腺经常显示出克隆性丢失， 11号染色体上EMEN1基因区域的等位基因。 EMEN1 一个基因作为肿瘤抑制基因，类似于视网膜母细胞瘤 基因 对散发性甲状旁腺腺瘤的分析显示，25%的患者表现为 相似区域的等位基因缺失。 因此， EMEN1基因也可能是许多散发性甲状旁腺疾病的一个促成因素。 腺瘤