A single fas gene mutation changes lupus onset, severity, location, and molecular abnormalities in mice.
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 Fas(lpr) 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. Fas(lpr) 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 Fas(lpr) 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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Hu
Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. shike888@gmail.com.
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Ke
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Wang
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Ran
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Chen
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Zhang
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Qiu
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Jiang
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Zou
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Zhang
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Cao
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Wen
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Fu
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Chen
D000375:Aging / Q000097:blood; D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D017370:Interleukin-11 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D019014:fas Receptor / Q000235:genetics*
C514936:CXCR4 protein, mouse; C491899:Fas protein, mouse; D017370:Interleukin-11; D019718:Receptors, CXCR4; D019014:fas Receptor; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse