GENETICS OF GLUCOCORTICOID INDUCED OSTEOPOROSIS IN MICE

糖皮质激素引起的小鼠骨质疏松症的遗传学

• 批准号: 6100430
• 负责人: ROBERT Daniel BLANK
• 金额: --
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6100430
• 关键词: animal breeding; chromosomes; dexamethasone; disease /disorder proneness /risk; drug adverse effect; family genetics; genetic mapping; genetic strain; genotype; glucocorticoids; laboratory mouse; osteoporosis; phenotype; single strand conformation polymorphism

Osteoporosis is a leading cause of morbidity and mortality of older individuals, but susceptibility to osteoporosis varies widely. Several lines of evidence suggest that genetic predisposition contributes about half of this variation. Although chronic glucocorticoid use can lead to a broad range of adverse effects including osteoporosis, these drugs are widely used for many medical conditions including the arthritides. As is the case with involutional osteoporosis, individuals vary widely in their susceptibility to glucocorticoid induced osteoporosis. This project tests the hypothesis that genetic predisposition contributes to glucocorticoid induced osteoporosis in mice. Its goal is to identify, map and ultimately clone genes mediating susceptibility to glucocorticoid induced osteoporosis in mice through the analysis of existing recombinant congenic strain sets. In the first stage of the work, the susceptibilities of the progenitors of the recombinant congenics to glucocorticoid induced osteoporosis, and secondarily other glucocorticoid toxicities, will be determined. In the second stage of the work, the recombinant congenic strain set whose progenitors are most divergent will be analyzed to identify chromosomal regions that harbor genes affecting glucocorticoid induced osteoporosis. In the third stage of the work further breeding will be performed to refine the mapping of the candidate genes and provide the necessary information for their positional cloning. Identifying mouse chromosome regions that contribute to osteoporosis will allow prediction of the corresponding human regions by synteny arguments and facilitate the design of human genetic studies of this problem.

骨质疏松症是老年人发病和死亡的主要原因 个体，但骨质疏松症的易感性差异很大。 几 一系列证据表明，遗传易感性有助于 一半的变化。 虽然长期使用糖皮质激素会导致 广泛的不良反应，包括骨质疏松症，这些药物是 广泛用于包括关节炎在内的许多医学病症。 如 在退化性骨质疏松症的情况下， 对糖皮质激素诱导的骨质疏松症易感。 该项目测试 遗传易感性有助于糖皮质激素的假设 诱发小鼠骨质疏松症。 它的目标是识别、绘制并最终 克隆介导糖皮质激素敏感性的基因 通过分析现有的重组同源基因， 应变集。 在工作的第一阶段， 糖皮质激素诱导的重组同源物的祖细胞 骨质疏松症，其次是其他糖皮质激素毒性， 测定 在工作的第二阶段，重组同源基因 将分析其祖细胞最趋异菌株组， 鉴定携带影响糖皮质激素基因的染色体区域 诱发骨质疏松症。 在第三阶段的工作中， 将进行细化候选基因的定位，并提供 定位克隆的必要信息 识别鼠标 导致骨质疏松症的染色体区域将允许预测 的相应的人类区域的共线性参数，并促进 设计人类遗传学研究这个问题。