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检测鼠巨细胞病毒(MCMV)诱导肝炎的小鼠血液的实验室诊断。

Laboratory diagnostics of murine blood for detection of mouse cytomegalovirus (MCMV)-induced hepatitis.

机构信息

Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.

出版信息

Sci Rep. 2018 Oct 4;8(1):14823. doi: 10.1038/s41598-018-33167-7.

Abstract

Mouse models are important and versatile tools to study mechanisms and novel therapies of human disease in vivo. Both, the number and the complexity of murine models are constantly increasing and modification of genes of interest as well as any exogenous challenge may lead to unanticipated biological effects. Laboratory diagnostics of blood samples provide a comprehensive and rapid screening for multiple organ function and are fundamental to detect human disease. Here, we adapt an array of laboratory medicine-based tests commonly used in humans to establish a platform for standardized, multi-parametric, and quality-controlled diagnostics of murine blood samples. We determined sex-dependent reference intervals of 51 commonly used laboratory medicine tests for samples obtained from the C57BL/6J mouse strain. As a proof of principle, we applied these diagnostic tests in a mouse cytomegalovirus (MCMV) infection model to screen for organ damage. Consistent with histopathological findings, plasma concentrations of liver-specific enzymes were elevated, supporting the diagnosis of a virus-induced hepatitis. Plasma activities of aminotransferases correlated with viral loads in livers at various days after MCMV infection and discriminated infected from non-infected animals. This study provides murine blood reference intervals of common laboratory medicine parameters and illustrates the use of these tests for diagnosis of infectious disease in experimental animals.

摘要

小鼠模型是研究人类疾病机制和新疗法的重要且多功能的工具。无论是模型的数量还是复杂性都在不断增加,而对感兴趣基因的修饰以及任何外源挑战都可能导致意想不到的生物学效应。血液样本的实验室诊断为多种器官功能提供了全面而快速的筛查,是检测人类疾病的基础。在这里,我们采用了一系列常用于人类的基于实验室医学的检测方法,建立了标准化、多参数和质量控制的小鼠血液样本诊断平台。我们确定了来自 C57BL/6J 品系小鼠的样本中 51 种常用实验室医学检测的性别依赖性参考区间。作为原理验证,我们将这些诊断检测应用于小鼠巨细胞病毒(MCMV)感染模型中,以筛选器官损伤。与组织病理学发现一致的是,肝脏特异性酶的血浆浓度升高,支持病毒诱导肝炎的诊断。血浆转氨酶活性与 MCMV 感染后不同天数肝脏中的病毒载量相关,并可区分感染和未感染的动物。本研究提供了常见实验室医学参数的小鼠血液参考区间,并说明了这些检测在实验动物感染性疾病诊断中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd3e/6172243/12553377df04/41598_2018_33167_Fig1_HTML.jpg

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