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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2006 ; 281
(7
): 4199-206
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Chronic wasting disease of elk and deer and Creutzfeldt-Jakob disease:
comparative analysis of the scrapie prion protein
#MMPMID16338930
Xie Z
; O'Rourke KI
; Dong Z
; Jenny AL
; Langenberg JA
; Belay ED
; Schonberger LB
; Petersen RB
; Zou W
; Kong Q
; Gambetti P
; Chen SG
J Biol Chem
2006[Feb]; 281
(7
): 4199-206
PMID16338930
show ga
Chronic wasting disease (CWD), a transmissible prion disease that affects elk and
deer, poses new challenges to animal and human health. Although the transmission
of CWD to humans has not been proven, it remains a possibility. If this were to
occur, it is important to know whether the "acquired" human prion disease would
show a phenotype including the scrapie prion protein (PrP(Sc)) features that
differ from those associated with human sporadic prion disease. In this study, we
have compared the pathological profiles and PrP(Sc) characteristics in brains of
CWD-affected elk and deer with those in subjects with sporadic Creutzfeldt-Jakob
disease (CJD), as well as CJD-affected subjects who might have been exposed to
CWD, using histopathology, immunohistochemistry, immunoblotting, conformation
stability assay, and N-terminal protein sequencing. Spongiform changes and
intense PrP(Sc) staining were present in several brain regions of CWD-affected
animals. Immunoblotting revealed three proteinase K (PK)-resistant bands in CWD,
representing different glycoforms of PrP(Sc). The unglycosylated PK-resistant
PrP(Sc) of CWD migrated at 21 kDa with an electrophoretic mobility similar to
that of type 1 human PrP(Sc) present in sporadic CJD affecting subjects
homozygous for methionine at codon 129 (sCJDMM1). N-terminal sequencing showed
that the PK cleavage site of PrP(Sc) in CWD occurred at residues 82 and 78,
similar to that of PrP(Sc) in sCJDMM1. Conformation stability assay also showed
no significant difference between elk CWD PrP(Sc) and the PrP(Sc) species
associated with sCJDMM1. However, there was a major difference in glycoform ratio
of PrP(Sc) between CWD and sCJDMM1 affecting both subjects potentially exposed to
CWD and non-exposed subjects. Moreover, PrP(Sc) of CWD exhibited a distinct
constellation of glycoforms distinguishable from that of sCJDMM1 in
two-dimensional immunoblots. These findings underline the importance of detailed
PrP(Sc) characterization in trying to detect novel forms of acquired prion
disease.