Genes contributing to prion pathogenesis
Tamgüney, Gültekin and Giles, Kurt and Glidden, David V. and Lessard, Pierre and Wille, Holger and Tremblay, Patrick and Groth, Darlene F. and Yehiely, Fruma and Korth, Carsten and Moore, Richard C. and Tatzelt, Jörg and Rubinstein, Eric and Boucheix, Claude and Yang, Xiaoping and Stanley, Pamela and Lisanti, Michael P. and Dwek, Raymond A. and Rudd, Pauline M. and Moskovitz, Jackob and Epstein, Charles J. and Cruz, Tracey Dawson and Kuziel, William A. and Maeda, Nobuyo and Sap, Jan and Ashe, Karen Hsiao and Carlson, George A. and Tesseur, Ina and Wyss-Coray, Tony and Mucke, Lennart and Weisgraber, Karl H. and Mahley, Robert W. and Cohen, Fred E. and Prusiner, Stanley B.,, 89, 1777-1788 (2008),
doi = https://doi.org/10.1099/vir.0.2008/001255-0,
publicationName = Microbiology Society,
issn = 0022-1317,
abstract= Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrPC) to a misfolded, pathogenic isoform (PrPSc). Prion inoculation experiments in mice expressing homologous PrPC molecules on different genetic backgrounds displayed different incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes, because their products either colocalize with PrP, are associated with Alzheimer's disease, are elevated during prion disease, or function in PrP-mediated signalling, PrP glycosylation, or protein maintenance. Whereas some of the candidates tested may have a role in the normal function of PrPC, our data show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and transgenic overexpression of human superoxide dismutase 1 (SOD1) prolonged incubation times by 13, 16 and 19 %, respectively.,
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