help button home button Am J Pathol JNCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taguchi, Y.
Right arrow Articles by Kitamoto, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taguchi, Y.
Right arrow Articles by Kitamoto, T.
(American Journal of Pathology. 2003;163:2585-2593.)
© 2003 American Society for Investigative Pathology

Animal Model

Humanized Knock-In Mice Expressing Chimeric Prion Protein Showed Varied Susceptibility to Different Human Prions

Yuzuru Taguchi*, Shirou Mohri{dagger}, James W. Ironside{ddagger}, Tamaki Muramoto*§ and Tetsuyuki Kitamoto*

From the Department of Neurological Science,*Tohoku University Graduate School of Medicine, Sendai, Japan; the Laboratory of Biomedicine,{dagger}Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; CREST,§Japan Science and Technology, Kawaguchi, Japan; and Creutzfeldt-Jakob Disease Surveillance Unit,{ddagger}Western General Hospital, Edinburgh, Scotland

Mice to which human prions efficiently transmit in short incubation periods are valuable not only as research tools of human prions but also as reliable diagnostic tools. We recently produced a line of knock-in mouse expressing a unique human-mouse chimeric PrP (Ki-ChM mouse), which has mouse-specific residues practically only at the C-terminal part after posttranslational modification, and here we attempted transmission of various human prions to assess the susceptibility profile of the mouse. Susceptibility varied considerably depending on prions inoculated: highly susceptible to MM1 and MV1 types of sporadic Creutzfeldt-Jakob disease (CJD), developing disease within ~150 days, familial CJD with M232R mutation, and dura graft-associated CJD (dCJD) without amyloid plaque; less susceptible to MM2-type sporadic CJD and variant CJD, with some mice lacking any sign of transmission; and totally resistant to VV2 type sporadic CJD and dCJD with amyloid plaque. The rather short incubation time achieved by Ki-ChM mice suggests new approaches to produce mice that develop prion disease with very short incubation periods. We compared the characteristic susceptibility profile of Ki-ChM with those of other precedent transgenic mice and discussed, including the prospects in developing genetically engineered mice susceptible to human prions.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Kobayashi, M. Asano, S. Mohri, and T. Kitamoto
Cross-sequence Transmission of Sporadic Creutzfeldt-Jakob Disease Creates a New Prion Strain
J. Biol. Chem., October 12, 2007; 282(41): 30022 - 30028.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. L. Lau, A. Y. Yam, M. M. D. Michelitsch, X. Wang, C. Gao, R. J. Goodson, R. Shimizu, G. Timoteo, J. Hall, A. Medina-Selby, et al.
Characterization of prion protein (PrP)-derived peptides that discriminate full-length PrPSc from PrPC
PNAS, July 10, 2007; 104(28): 11551 - 11556.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
A. Kobayashi, S. Satoh, J. W. Ironside, S. Mohri, and T. Kitamoto
Type 1 and type 2 human PrPSc have different aggregation sizes in methionine homozygotes with sporadic, iatrogenic and variant Creutzfeldt-Jakob disease
J. Gen. Virol., January 1, 2005; 86(1): 237 - 240.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.