Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

作者：Bishop Matthew T; Will Robert G; Manson Jean C^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(26): 12005-12010.

DOI：10.1073/pnas.1004688107

• codon 129 genotype
• mouse model
• prion disease
• transmission strains

The biological determinants of the phenotypic variation in sporadic Creutzfeldt-Jakob disease (sCJD) are unknown. To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrPSc) can be combined to formsix subgroups(MM1, MM2, MV1, MV2, VV1, and VV2). This classification largely correlates with the known variation in the clinical and pathological features of sCJD, with the MM1 and MV1 cases representing the "classic" phenotype of sCJD. To address how this classification relates to different strains of sCJD we have inoculated each subgroup of sCJD to a panel of mice expressing different forms of the human PRNP gene (129MM, 129VV, and 129MV). We have established that all subtypes are transmissible to at least one genotype of mouse, and both agent and host factors determine transmission efficiency and the form of PrP(Sc) deposited in the brain. Moreover, we have identified four distinct strains of sCJD using our in vivo strain typing panel.

• 出版日期2010-6-29