摘要
虽然遗传在系统性红斑狼疮(SLE)及其症状的变化和发展过程中起着重要作用,且基因突变和疾病状态之间的精确关系也不好理解。本文阐述了基因突变对疾病病因的影响。在遗传背景相同但Fas基因不同的条件下,我们检测了系统性红斑狼疮的两个鼠标模型。具有Faslpr这种基因的老鼠可发展为严重的系统性红斑狼疮、肾脏功能障碍及肺和肾脏的炎症反应。相比之下,具有Fas +基因的老鼠会在肝和关节中显示疾病相关的异常情况。从用炎性疾病标记两组老鼠不同的器官来看,Faslpr老鼠比Fas +小鼠在肾脏和肺中分别显示更大的MMP信号和IL-11信号。Fas +小鼠比Faslpr老鼠在膝盖中具有更高IL-11信号强度,在肝脏中具有更高的CXCR4信号强度。我们得出结论,为例证疾病复杂性,需要个性化且有针对性的治疗方案。本研究的优势和局限性在于:Fas基因在此类疾病中的特征基因,但在分子组件研究中仍需更多的临床资料。
关键词:
Current Molecular Medicine
Title:A Single Fas Gene Mutation Changes Lupus Onset, Severity, Location, and Molecular Abnormalities in Mice
Volume: 15 Issue: 4
Author(s): S. Hu, S. Ke, W. Wang, H. Ran, M. Chen, F. Zhang, X. Qiu, M. Jiang, C. Zou, R. Zhang, L. Cao, Y. Wen, R. Fu and C. Chen
Affiliation:
关键词:
摘要: Although genetic predisposition plays a major role in the progression of systemic lupus erythematosus (SLE) and its variation in symptoms, the precise relationships between genetic changes and disease status are not well understood. Here, to demonstrate the effect of a single gene mutation on disease etiology, we examined two mouse models of SLE with the same genetic background but different Fas genes. Mice with the Faslpr gene developed severe SLE with renal dysfunction and inflammatory responses in the lung and kidney. By contrast, mice with the Fas+ gene showed disease-related abnormalities in the liver and joints. Patterns of inflammatory disease markers differed across organs between the two lines of mice. Faslpr mice showed greater MMP signals in the kidney and IL-11 signals in the lung than Fas+ mice. Fas+ mice had higher IL-11 signal intensity in the knee region and higher CXCR4 signal intensity in the liver than Faslpr mice. Our results exemplify the complexity of disease and suggest the need for individualized target-specific treatment regimens.
Strengths and Limitations of this Study: Fas gene is a well characterized gene in this disease. The molecular components in human disease need more clinical data.
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S. Hu, S. Ke, W. Wang, H. Ran, M. Chen, F. Zhang, X. Qiu, M. Jiang, C. Zou, R. Zhang, L. Cao, Y. Wen, R. Fu and C. Chen , A Single Fas Gene Mutation Changes Lupus Onset, Severity, Location, and Molecular Abnormalities in Mice, Current Molecular Medicine 2015; 15 (4) . https://dx.doi.org/10.2174/1566524015666150505162638
DOI https://dx.doi.org/10.2174/1566524015666150505162638 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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