Genes contributing to prion pathogenesis.

Gültekin Tamgüney; Kurt Giles; David V Glidden; Pierre Lessard; Holger Wille; Patrick Tremblay; Darlene F Groth; Fruma Yehiely; Carsten Korth; Richard C Moore; Jörg Tatzelt; Eric Rubinstein; Claude Boucheix; Xiaoping Yang; Pamela Stanley; Michael P Lisanti; Raymond A Dwek; Pauline M Rudd; Jackob Moskovitz; Charles J Epstein; Tracey Dawson Cruz; William A Kuziel; Nobuyo Maeda; Jan Sap; Karen Hsiao Ashe; George A Carlson; Ina Tesseur; Tony Wyss-Coray; Lennart Mucke; Karl H Weisgraber; Robert W Mahley; Fred E Cohen; Stanley B Prusiner

doi:10.1099/vir.0.2008/001255-0

Genes contributing to prion pathogenesis.

Gültekin Tamgüney, Kurt Giles, David V Glidden, Pierre Lessard, Holger Wille, Patrick Tremblay, Darlene F Groth, Fruma Yehiely, Carsten Korth, Richard C Moore, Jörg Tatzelt, Eric Rubinstein, Claude Boucheix, Xiaoping Yang, Pamela Stanley, Michael P Lisanti, Raymond A Dwek, Pauline M Rudd, Jackob Moskovitz, Charles J EpsteinTracey Dawson Cruz, William A Kuziel, Nobuyo Maeda, Jan Sap, Karen Hsiao Ashe, George A Carlson, Ina Tesseur, Tony Wyss-Coray, Lennart Mucke, Karl H Weisgraber, Robert W Mahley, Fred E Cohen, Stanley B Prusiner

Department of Biomedical Sciences

95 Citations (Scopus)

Abstract

Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice expressing homologous PrP(C) 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 PrP(C), 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.

Original language	English
Journal	Journal of General Virology
Volume	89
Issue number	Pt 7
Pages (from-to)	1777-88
Number of pages	11
ISSN	0022-1317
DOIs	https://doi.org/10.1099/vir.0.2008/001255-0
Publication status	Published - 2008

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1099/vir.0.2008/001255-0

Cite this

Tamgüney, G., Giles, K., Glidden, D. V., Lessard, P., Wille, H., Tremblay, P., Groth, D. F., Yehiely, F., Korth, C., Moore, R. C., Tatzelt, J., Rubinstein, E., Boucheix, C., Yang, X., Stanley, P., Lisanti, M. P., Dwek, R. A., Rudd, P. M., Moskovitz, J., ... Prusiner, S. B. (2008). Genes contributing to prion pathogenesis. Journal of General Virology, 89(Pt 7), 1777-88. https://doi.org/10.1099/vir.0.2008/001255-0

Tamgüney, G, Giles, K, Glidden, DV, Lessard, P, Wille, H, Tremblay, P, Groth, DF, Yehiely, F, Korth, C, Moore, RC, Tatzelt, J, Rubinstein, E, Boucheix, C, Yang, X, Stanley, P, Lisanti, MP, Dwek, RA, Rudd, PM, Moskovitz, J, Epstein, CJ, Cruz, TD, Kuziel, WA, Maeda, N, Sap, J, Ashe, KH, Carlson, GA, Tesseur, I, Wyss-Coray, T, Mucke, L, Weisgraber, KH, Mahley, RW, Cohen, FE & Prusiner, SB 2008, 'Genes contributing to prion pathogenesis.', Journal of General Virology, vol. 89, no. Pt 7, pp. 1777-88. https://doi.org/10.1099/vir.0.2008/001255-0

@article{568a202054a611dd8d9f000ea68e967b,

title = "Genes contributing to prion pathogenesis.",

abstract = "Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice expressing homologous PrP(C) 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 PrP(C), 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.",

author = "G{\"u}ltekin Tamg{\"u}ney and Kurt Giles and Glidden, {David V} and Pierre Lessard and Holger Wille and Patrick Tremblay and Groth, {Darlene F} and Fruma Yehiely and Carsten Korth and Moore, {Richard C} and J{\"o}rg Tatzelt and Eric Rubinstein and Claude Boucheix and Xiaoping Yang and Pamela Stanley and Lisanti, {Michael P} and Dwek, {Raymond A} and Rudd, {Pauline M} and Jackob Moskovitz and Epstein, {Charles J} and Cruz, {Tracey Dawson} and Kuziel, {William A} and Nobuyo Maeda and Jan Sap and Ashe, {Karen Hsiao} and Carlson, {George A} and Ina Tesseur and Tony Wyss-Coray and Lennart Mucke and Weisgraber, {Karl H} and Mahley, {Robert W} and Cohen, {Fred E} and Prusiner, {Stanley B}",

year = "2008",

doi = "10.1099/vir.0.2008/001255-0",

language = "English",

volume = "89",

pages = "1777--88",

journal = "Journal of General Virology",

issn = "0022-1317",

publisher = "Society for General Microbiology",

number = "Pt 7",

}

TY - JOUR

T1 - Genes contributing to prion pathogenesis.

AU - Tamgüney, Gültekin

AU - Giles, Kurt

AU - Glidden, David V

AU - Lessard, Pierre

AU - Wille, Holger

AU - Tremblay, Patrick

AU - Groth, Darlene F

AU - Yehiely, Fruma

AU - Korth, Carsten

AU - Moore, Richard C

AU - Tatzelt, Jörg

AU - Rubinstein, Eric

AU - Boucheix, Claude

AU - Yang, Xiaoping

AU - Stanley, Pamela

AU - Lisanti, Michael P

AU - Dwek, Raymond A

AU - Rudd, Pauline M

AU - Moskovitz, Jackob

AU - Epstein, Charles J

AU - Cruz, Tracey Dawson

AU - Kuziel, William A

AU - Maeda, Nobuyo

AU - Sap, Jan

AU - Ashe, Karen Hsiao

AU - Carlson, George A

AU - Tesseur, Ina

AU - Wyss-Coray, Tony

AU - Mucke, Lennart

AU - Weisgraber, Karl H

AU - Mahley, Robert W

AU - Cohen, Fred E

AU - Prusiner, Stanley B

PY - 2008

Y1 - 2008

N2 - Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice expressing homologous PrP(C) 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 PrP(C), 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.

AB - Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice expressing homologous PrP(C) 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 PrP(C), 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.

U2 - 10.1099/vir.0.2008/001255-0

DO - 10.1099/vir.0.2008/001255-0

M3 - Journal article

C2 - 18559949

SN - 0022-1317

VL - 89

SP - 1777

EP - 1788

JO - Journal of General Virology

JF - Journal of General Virology

IS - Pt 7

ER -

Genes contributing to prion pathogenesis.

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this