Allelic origin of the abnormal prion protein isoform in familial prion diseases. Nat Med 1997 Sep;3(9):1009-15
Date
09/01/1997Pubmed ID
9288728DOI
10.1038/nm0997-1009Scopus ID
2-s2.0-0030768832 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
The hallmark of prion diseases is the presence of an aberrant isoform of the prion protein (PrP(res)) that is insoluble in nondenaturing detergents and resistant to proteases. We investigated the allelic origin of PrP(res) in brains of subjects heterozygous for the D178N mutation linked to fatal familial insomnia (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD178), as well as for insertional mutations associated with another CJD subtype. We found that in FFI and CJD178 subjects, only mutant PrP was detergent-insoluble and protease-resistant. Therefore, PrP(res) derives exclusively from the mutant allele carrying the D178N mutation. In contrast, in the CJD subtype harboring insertional mutations, wild-type PrP was also detergent-insoluble and likely to be protease-resistant. Our findings indicate that the participation of the wild-type PrP in the formation of PrP(res) depends on the type of mutations, providing an insight into the molecular mechanisms underlying the phenotypic heterogeneity in familial prion diseases.
Author List
Chen SG, Parchi P, Brown P, Capellari S, Zou W, Cochran EJ, Vnencak-Jones CL, Julien J, Vital C, Mikol J, Lugaresi E, Autilio-Gambetti L, Gambetti PAuthor
Elizabeth J. Cochran MD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesCreutzfeldt-Jakob Syndrome
Detergents
Endopeptidases
Heterozygote
Humans
Mutation
Peptide Mapping
Phenotype
Point Mutation
Prion Diseases
Prions
Sleep Initiation and Maintenance Disorders
Solubility