Prion-induced amyloid heart disease with high blood infectivity in transgenic mice.
We investigated extraneural manifestations in scrapie-infected transgenic mice expressing prion protein lacking the glycophosphatydylinositol membrane anchor. In the brain, blood, and heart, both abnormal protease-resistant prion protein (PrPres) and prion infectivity were readily detected by immunoblot and by inoculation into nontransgenic recipients. The titer of infectious scrapie in blood plasma exceeded 10(7) 50% infectious doses per milliliter. The hearts of these transgenic mice contained PrPres-positive amyloid deposits that led to myocardial stiffness and cardiac disease.
Trifilo
Matthew J
MJ
Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, Scripps Research Institute, La Jolla, CA 92037, USA.
Yajima
Toshitaka
T
Gu
Yusu
Y
Dalton
Nancy
N
Peterson
Kirk L
KL
Race
Richard E
RE
Meade-White
Kimberly
K
Portis
John L
JL
Masliah
Eliezer
E
Knowlton
Kirk U
KU
Chesebro
Bruce
B
Oldstone
Michael B A
MB
D000682:Amyloid / Q000032:analysis*; D000686:Amyloidosis / Q000097:blood / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D006328:Cardiac Catheterization; D003331:Coronary Vessels / Q000737:chemistry / Q000473:pathology; D004195:Disease Models, Animal; D017261:Glycosylphosphatidylinositols; D006331:Heart Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D006334:Heart Function Tests; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008833:Microcirculation / Q000737:chemistry / Q000473:pathology; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology*; D018621:PrPC Proteins / Q000737:chemistry; D018620:PrPSc Proteins / Q000032:analysis* / Q000097:blood; D012608:Scrapie / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D013194:Staining and Labeling; D013997:Time Factors
D000682:Amyloid; D017261:Glycosylphosphatidylinositols; D018621:PrPC Proteins; D018620:PrPSc Proteins