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From: TSS ()
Subject: Polymorphisms at codons 108 and 189 in murine PrP play distinct roles in the control of scrapie incubation time
Date: February 19, 2005 at 9:00 am PST

-------- Original Message --------
Subject: Polymorphisms at codons 108 and 189 in murine PrP play distinct roles in the control of scrapie incubation time
Date: Fri, 18 Feb 2005 20:15:55 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE


##################### Bovine Spongiform Encephalopathy #####################

© 2005 Society for
General Microbiology


Polymorphisms at codons 108 and 189 in murine PrP play distinct
roles in the control of scrapie incubation time

Rona M. Barron1, Herbert Baybutt1, Nadia L. Tuzi1, James
McCormack1,{dagger} , Declan King1, Richard C. Moore2,{ddagger} , David
W. Melton3 and Jean C. Manson1

1 Neuropathogenesis Unit, Institute for Animal Health, Ogston Building,
West Mains Road, Edinburgh EH9 3JF, UK
2 Institute of Cell and Molecular Biology, University of Edinburgh,
Edinburgh, UK
3 Sir Alastair Currie Cancer Research UK Laboratories, Molecular
Medicine Centre, University of Edinburgh, Western General Hospital,
Edinburgh, UK

Correspondence
Rona M. Barron
rona.barron@bbsrc.ac.uk

Susceptibility to transmissible spongiform encephalopathies (TSEs) is
associated strongly with PrP polymorphisms in humans, sheep and rodents.
In mice, scrapie incubation time is controlled by polymorphisms at PrP
codons 108 (leucine or phenylalanine) and 189 (threonine or valine), but
the precise role of each polymorphism in the control of disease is
unknown. The L108F and T189V polymorphisms are present in distinct
structural regions of PrP and thus provide an excellent model with which
to investigate the role of PrP structure and gene variation in TSEs. Two
unique lines of transgenic mice, in which 108F and 189V have been
targeted separately into the endogenous murine Prnpa gene, have been
produced. TSE inoculation of inbred lines of mice expressing all allelic
combinations at codons 108 and 189 has revealed a complex relationship
between PrP allele and incubation time. It has been established that
both codons 108 and 189 control TSE incubation time, and that each
polymorphism plays a distinct role in the disease process. Comparison of
ME7 incubation times in mouse lines that are heterozygous at both codons
has also identified a previously unrecognized intramolecular interaction
between PrP codons 108 and 189.

Published online ahead of print on 5 January 2005 as DOI
10.1099/vir.0.80525-0.

A supplementary figure showing ME7 and 301V incubation times in mice
expressing codon 108 and 189 polymorphisms is available in JGV Online.

{dagger} Present address: Department for Environment, Food and Rural
Affairs (DEFRA), Veterinary Research Division, TSE Research Unit, Dean
Stanley Street, London, UK.

{ddagger} Present address: Department of Genetics and Genomics, Roslin
Institute, Edinburgh, UK.

http://vir.sgmjournals.org/cgi/content/abstract/86/3/859?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1108778143595_1188&stored_search=&FIRSTINDEX=0&volume=86&issue=3&search_url=http%3A%2F%2Fvir.sgmjournals.org%2Fcgi%2Fsearch

TSS

######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########





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