期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 35, 页码 15002-15006出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907339106
关键词
astrocytic gliosis; bioassay; GFAP; neurodegeneration
资金
- Larry L. Hillblom Foundation fellowship
- National Institutes of Health [AG02132, AG023501, AG10770]
- Michael Homer Foundation
- NATIONAL INSTITUTE ON AGING [P50AG023501, P01AG010770, P01AG002132] Funding Source: NIH RePORTER
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.
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