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Scrapie‐Infected Mice and PrP Knockout Mice Share Abnormal Localization and Activity of Neuronal Nitric Oxide Synthase
Author(s) -
Keshet Gilmor I.,
Ovadia Haim,
Taraboulos Albert,
Gabizon Ruth
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0721224.x
Subject(s) - scrapie , nitric oxide synthase , biology , knockout mouse , gene isoform , microbiology and biotechnology , glycolipid , nitric oxide , virology , prion protein , immunology , receptor , biochemistry , endocrinology , pathology , gene , medicine , disease
: PrP Sc , the only identified component of thescrapie prion, is a conformational isoform of PrP c . Thephysiological role of PrP c , a glycolipid‐anchored glycoprotein, isstill unknown. We have shown previously that neuronal nitric oxide synthase(nNOS) activity is impaired in the brains of mice sick with experimentalscrapie as well as in scrapie‐infected neuroblastoma cells. In this work weinvestigated the cell localization of nNOS in brains of wild‐type andscrapie‐infected mice as well as in mice in which the PrP gene was ablated. Wenow report that whereas in wild‐type mice, nNOS, like PrP c , isassociated with detergent‐insoluble cholesterol‐rich membranous microdomains(rafts), this is not the case in brains of scrapie‐infected or in those ofadult PrP % mice. Also, adult PrP % , like scrapie‐infectedmice, show reduced nNOS activity. We suggest that PrP c may play arole in the targeting of nNOS to its proper subcellular localization. Thesimilarities of nNOS properties in PrP % as compared withscrapie‐infected mice suggest that at least this role of PrP c may be impaired in scrapie‐infected brains.