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Measuring prions by bioluminescence imaging

机译:通过生物发光成像测量病毒

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摘要

Prions are infectious proteins that cause fatal neurodegenerative diseases. Because astrocytic gliosis marked by the deposition of fibrils composed of GFAP is a prominent feature of prion disease, we asked whether GFAP might be used as a surrogate marker for prions. To interrogate this posit, we inoculated prions into trans-genic (Tg) mice expressing luciferase (luc) under the GFAP gene (Gfap) promoter, denoted Tg(Gfap-luc) mice. Weekly noninvasive, bioluminescence imaging (BLI) detected an increase in light emitted from the brains of Tg(Gfap-luc) mice at ≈55 d after inoculation and ≈62 d before neurologic deficits appeared. To determine whether BLI could be used as a proxy bioassay for prion infectivity, we performed endpoint titrations of prions in Tg(Gfap-luc) mice. BLI bioassays were as or more sensitive than those determined by the onset of neurological dysfunction, and were completed in approximately half the time. Our studies argue that BLI is likely to be a suitable surrogate for measuring prion infectivity, and might be useful in the study of Tg mouse models for other neurodegenerative illnesses.
机译:ions病毒是引起致命性神经退行性疾病的传染性蛋白质。由于以GFAP组成的原纤维沉积为特征的星形胶质细胞胶质增生是病毒疾病的主要特征,因此我们询问GFAP是否可以用作病毒的替代标记。为了询问该位置,我们将病毒接种到在GFAP基因(Gfap)启动子下表达荧光素酶(luc)的转基因(Tg)小鼠中,表示为Tg(Gfap-luc)小鼠。每周无创生物发光成像(BLI)在接种后≈55d和神经功能缺损出现之前的≈62d时检测到Tg(Gfap-luc)小鼠大脑发射的光增加。为了确定BLI是否可以用作病毒感染性的替代生物测定,我们在Tg(Gfap-luc)小鼠中进行了ions病毒的终点滴定。 BLI生物测定的灵敏度与神经功能障碍发作时确定的灵敏度相同或更高,大约需要一半的时间才能完成。我们的研究认为BLI可能是衡量病毒感染性的合适替代品,并且可能在研究其他神经退行性疾病的Tg小鼠模型中有用。

著录项

  • 来源
  • 作者单位

    Institute for Neurodegenerative Diseases and Departments , University of California, San Francisco, CA 94143 Institute for Neurodegenerative Diseases and Neurology , University of California, San Francisco, CA 94143;

    Caliper Life Sciences, Alameda, CA 94501;

    Institute for Neurodegenerative Diseases and Departments , University of California, San Francisco, CA 94143 Institute for Neurodegenerative Diseases and Neurology , University of California, San Francisco, CA 94143;

    Pathology, University of California, San Francisco, CA 94143;

    Institute for Neurodegenerative Diseases and Departments , University of California, San Francisco, CA 94143 Pathology, University of California, San Francisco, CA 94143;

    Institute for Neurodegenerative Diseases and Departments , University of California, San Francisco, CA 94143 Institute for Neurodegenerative Diseases and Neurology , University of California, San Francisco, CA 94143;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    astrocytic gliosis; bioassay; GFAP; neurodegeneration;

    机译:星形细胞胶质增生;生物分析;GFAP;神经变性;

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