title: Measuring prions by bioluminescence imaging.
abstract: 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 approximately 55 d after inoculation and approximately 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.
authors.affiliation: Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: Gültekin
authors.initials: G
authors.lastname: Tamgüney
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Francis
authors.forename: Kurt
authors.initials: K
authors.lastname: Giles
authors.forename: Azucena
authors.initials: A
authors.lastname: Lemus
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017930:Genes, Reporter; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000032:analysis* / Q000378:metabolism
chemical_list: D011328:Prions; D008156:Luciferases
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