Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice

Sarah E. Lloyd, James B. Uphill, Paul V. Targonski, Elizabeth M C Fisher, John Collinge

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Prion diseases are fatal neurodegenerative disorders of humans and animals, which include bovine spongiform encephalopathy (BSE) and its human form, variant Creutzfeldt-Jakob disease (vCJD). They are characterized by a prolonged incubation period, which is known to be influenced by polymorphisms in the prion protein gene. Previous studies of inbred mice have demonstrated that additional genetic loci also contribute to the observed variation in incubation period. However, a substantial transmission barrier between cow and mouse complicates studies using BSE. As a result, primary transmissions display large variations in incubation period and not all animals develop clinical signs of disease. To identify quantitative trait loci for BSE without the presence of a transmission barrier, we analysed 124 animals from an F2 intercross between CAST/Ei and NZW/OlaHsd mice and challenged them intracerebrally with a strain of BSE that was passaged twice through C57BL/6OlaHsd mice. Interval mapping identified two highly significant linked regions on chromosomes 2 and 11 with peak lod scores of 6.34 and 4.77, respectively. Composite interval mapping suggests that chromosome 2 includes three linked quantitative trait loci. Loci in the same position on chromosomes 2 and 11 were also identified in a previous study using the same mouse cross but infected with Chandler/RML scrapie prions. If these are the same loci, it suggests that these loci may be influencing incubation time independently of prion strain. This provides hope that it may be possible to identify human quantitative trait loci for prion incubation time using mouse models that may allow identification of at-risk individuals and the discovery of novel therapeutic targets.

Original languageEnglish (US)
Pages (from-to)77-81
Number of pages5
JournalNeurogenetics
Volume4
Issue number2
DOIs
StatePublished - Oct 2002

Fingerprint

Bovine Spongiform Encephalopathy
Genetic Loci
Chromosomes, Human, Pair 2
Prions
Quantitative Trait Loci
Chromosomes, Human, Pair 11
Lod Score
Scrapie
Creutzfeldt-Jakob Syndrome
Prion Diseases
Inbred C57BL Mouse
Neurodegenerative Diseases
Genes

Keywords

  • Bovine spongiform encephalopathy
  • Chromosome 11
  • Chromosome 2
  • Incubation time
  • Linkage

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice. / Lloyd, Sarah E.; Uphill, James B.; Targonski, Paul V.; Fisher, Elizabeth M C; Collinge, John.

In: Neurogenetics, Vol. 4, No. 2, 10.2002, p. 77-81.

Research output: Contribution to journalArticle

Lloyd, Sarah E. ; Uphill, James B. ; Targonski, Paul V. ; Fisher, Elizabeth M C ; Collinge, John. / Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice. In: Neurogenetics. 2002 ; Vol. 4, No. 2. pp. 77-81.
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