Measuring prions by bioluminescence imaging

被引:46
作者
Tamgueney, Gueltekin [1 ,2 ]
Francis, Kevin P. [4 ]
Giles, Kurt [1 ,2 ]
Lemus, Azucena [3 ]
DeArmond, Stephen J. [1 ,3 ]
Prusiner, Stanley B. [1 ,2 ]
机构
[1] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[4] Caliper Life Sci, Alameda, CA 94501 USA
基金
美国国家卫生研究院;
关键词
astrocytic gliosis; bioassay; GFAP; neurodegeneration; FIBRILLARY ACIDIC PROTEIN; CREUTZFELDT-JAKOB-DISEASE; TRANSGENIC MICE; SCRAPIE PRION; INCUBATION PERIOD; GENE-EXPRESSION; GROWTH-FACTORS; MOUSE SCRAPIE; IN-VIVO; ASTROCYTE;
D O I
10.1073/pnas.0907339106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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 transgenic (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 approximate to 55 d after inoculation and approximate to 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.
引用
收藏
页码:15002 / 15006
页数:5
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