Genetics. Published Articles Ahead of Print: August 20, 2008, Copyright © 2008
doi:10.1534/genetics.108.090894


A more recent version of this article appeared on September 1, 2008.

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Investigation of Mcp1 as a Quantitative Trait Gene for Prion Disease Incubation Time in Mouse

Marie O'Shea 1, Emma G. Maytham 1, Jackie M. Linehan 1, Sebastian Brandner 1, John Collinge 1 and Sarah Lloyd 1*

1 MRC Prion Unit

* To whom correspondence should be addressed. E-mail: s.lloyd{at}prion.ucl.ac.uk.

Submitted on May 1, 2008
Revised on May 22, 2008
Accepted on 20 June 2008


Abstract

The genetic basis of prion disease incubation time is principally determined by polymorphisms in the prion protein gene, Prnp. However, it is now known that other genetic factors are important. Several quantitative trait loci (QTL) have been identified across the genome including a broad region of linkage on Mmu11. Monocyte chemoattractant protein 1 (MCP-1) maps to this region and has been associated with microglial activation and reduced survival in the ME7 mouse scrapie model of prion disease. We have identified 10 polymorphisms, 3 of which are nonsynonomous, in Mcp1 between "long" (CAST) and "short" (SJL or NZW) incubation time mouse strains. Crosses between these strains and Mcp1-/- mice inoculated with the Chandler/RML mouse scrapie prion strain formed the basis of a quantitative complementation test. In these models loss of Mcp1 did not show an increase in incubation time suggesting that the effects of Mcp1 may be specific to the ME7 prion strain and that Mcp1 does not contribute to the QTL described on Mmu11.

Key Words: Mcp1, Quantitative Trait Gene, microglia, prion disease incubation time, prion strain