Investigation of mcp1 as a quantitative trait gene for prion disease incubation time in mouse.
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.
O'Shea
Marie
M
Medical Research Council Prion Unit and Department of Neurodegenerative Diseases, Institute of Neurology, University College, London WC1N 3BG, United Kingdom.
Maytham
Emma G
EG
Linehan
Jackie M
JM
Brandner
Sebastian
S
Collinge
John
J
Lloyd
Sarah E
SE
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics* / Q000502:physiology*; D003433:Crosses, Genetic; D005260:Female; D005816:Genetic Complementation Test; D008040:Genetic Linkage; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D017096:Prion Diseases / Q000175:diagnosis / Q000235:genetics*; D040641:Quantitative Trait Loci
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2