Glycosylation-related gene expression profiling in the brain and spleen of scrapie-affected mouse.
A central event in the formation of infectious prions is the conformational change of a host-encoded glycoprotein, PrP(C), into a pathogenic isoform, PrP(Sc). The molecular requirements for efficient PrP conversion remain unknown. Altered glycosylation has been linked to various pathologies and the N-glycans harbored by two prion protein isoforms are different. In order to search for glycosylation-related genes that could mark prion infection, we used a glycosylation-dedicated microarray that allowed the simultaneous analysis of the expression of 165 glycosylation-related genes encoding proteins of the glycosyltransferase, glycosidase, lectin, and sulfotransferase families to compare the gene expression profiles of normal and scrapie-infected mouse brain and spleen. Eight genes were found upregulated in "scrapie brain" at the final state of the disease. In the spleen, five genes presented a modified expression. Three genes were also upregulated in the spleen of infected mice, and two (Pigq and St3gal5) downregulated. All changes were confirmed by qPCR and biochemical analyses applied to Pigq and St3gal5 proteins.
Guillerme-Bosselut
Florence
F
INRA, UMR1061 Génétique Moléculaire Animale, Université de Limoges, Limoges, France.
Forestier
Lionel
L
Jayat-Vignoles
Chantal
C
Vilotte
Jean-Luc
JL
Popa
Iuliana
I
Portoukalian
Jacques
J
Le Dur
Annick
A
Laude
Hubert
H
Julien
Raymond
R
Gallet
Paul-François
PF
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D051379:Mice; D046228:Microarray Analysis; D018620:PrPSc Proteins / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*
D006023:Glycoproteins; D018620:PrPSc Proteins