...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach
【24h】

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach

机译：与疾病相关的扰动后法布里病鼠模型的基因组异常，一种系统生物学方法

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Fabry disease is a disorder of α-D-galactosyl-containing glycolipids resulting from a deficiency of α-galactosidase A. Patients have a poorly understood vascular dysregulation. We hypothesized that disease-related perturbation by using enzyme replacement therapy in the murine model of Fabry disease would provide insight into abnormal biological processes in Fabry disease. Gene expression analyses of the heart, aorta, and liver of male α-galactosidase A knockout mice 28 weeks of age were compared with that of WT mice. Microarray analyses were performed before and after six weekly injections of α-galactosidase A. Alteration of Rpgrip1 ranked highest statistically in all three organs when knockout mice were compared with WT, and its splice variants responded in a unique way to α-galactosidase A. Enzyme replacement therapy tended to not only normalize gene expression, e.g., reduce the overexpression of securin, but also specifically modified gene expression in each tissue examined. Following multiple comparison analysis, gene expression correlation graphs were constructed, and a priori hypotheses were examined by using structural equation modeling. This systems biology approach demonstrated multiple and complex parallel cellular abnormalities in Fabry disease. These abnormalities form the basis for informed, in a Bayesian sense, sequential, hypothesis-driven research that can be subsequently tested experimentally.
机译：法布里病是由α-半乳糖苷酶A缺乏引起的含α-D-半乳糖基糖脂的疾病。患者对血管的调节异常了解不足。我们假设在法布里病的鼠模型中使用酶替代疗法与疾病相关的扰动将提供对法布里病异常生物学过程的洞察力。比较了28周龄雄性α-半乳糖苷酶A基因敲除小鼠的心脏，主动脉和肝脏的基因表达分析与WT小鼠的基因表达分析。在每周注射α-半乳糖苷酶A之前和之后进行了微阵列分析。当敲除小鼠与WT进行比较时，Rpgrip1的改变在所有三个器官中的统计学上均排名最高，其剪接变体以独特的方式对α-半乳糖苷酶A做出反应。替代疗法不仅倾向于使基因表达正常化（例如减少安全性蛋白的过表达），而且还倾向于在每个检查的组织中特异性修饰基因表达。经过多次比较分析，构建了基因表达相关图，并使用结构方程模型检查了先验假设。该系统生物学方法证明了法布里病中多种复杂的平行细胞异常。这些异常现象构成了以贝叶斯（Bayes）方式进行的，以假设为依据的先后顺序研究的基础，该研究随后可以通过实验进行检验。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号