Originally published as Genetics Published Articles Ahead of Print on August 20, 2008.

Genetics, Vol. 180, 559-566, September 2008, Copyright © 2008
doi:10.1534/genetics.108.090894

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

Marie O'Shea, Emma G. Maytham, Jackie M. Linehan, Sebastian Brandner, John Collinge and Sarah E. Lloyd1

Medical Research Council Prion Unit and Department of Neurodegenerative Diseases, Institute of Neurology, University College, London WC1N 3BG, United Kingdom

1 Corresponding author: Medical Research Council Prion Unit, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
E-mail: s.lloyd{at}prion.ucl.ac.uk

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.