Genetic control of amyloid plaque production and incubation period in scrapie-infected mice

Abstract

The extent of amyloid plaque production was investigated in three inbred mouse strains carrying the p7 allele of the scrapie incubation (Sinc) gene (VM, IM and MB). With either ME7 or 87V scrapie, many more plaques were seen in the MB strain than in VM or IM mice. A backcrossing experiment using 87V suggested the involvement of more than one gene. Within this backcrossing experiment there was a positive correlation between mean plaque count and mean incubation period for the various strains and crosses. Also male mice tended to have higher plaque counts and longer incubation periods than female mice of the same genotype. These results suggest that some of the genes controlling minor variation in the incubation period also influence plaque production. This is consistent with previous evidence that the number of amyloid plaques depends, to some extent, on the duration of agent replication within the brain. This study has also identified a high plaque model (MB mice infected with 87V) for future investigation of the nature of the amyloid protein.