title: Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice.
abstract: The incubation period (IP) and the neuropathology of transmissible spongiform encephalopathies (TSEs) have been extensively used to distinguish prion isolates (or strains) inoculated into panels of inbred mouse strains. Such studies have shown that the bovine spongiform encephalopathy (BSE) agent is indistinguishable from the agent causing variant Creutzfeldt-Jakob disease (vCJD), but differs from isolates of sporadic CJD, reinforcing the idea that the vCJD epidemic in Britain results from consumption of contaminated beef products. We present a mouse model for genetic and environmental factors that modify the incubation period of BSE cross-species transmission. We have used two mouse strains that carry the same prion protein (PrP) allele, but display a 100-day difference in their mean IP following intracerebral inoculation with primary BSE isolate. We report genetic effects on IP that map to four chromosomal regions, and in addition we find significant factors of host environment, namely the age of the host's mother, the age of the host at infection, and an X-cytoplasm interaction in the host.
authors.affiliation: Medical Research Council Human Genetics Unit, Crewe Road, Western General Hospital, EH4 2XU Edinburgh, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Manolakou
authors.forename: J
authors.initials: J
authors.lastname: Beaton
authors.forename: I
authors.initials: I
authors.lastname: McConnell
authors.forename: C
authors.initials: C
authors.lastname: Farquar
authors.forename: J
authors.initials: J
authors.lastname: Manson
authors.forename: N D
authors.initials: ND
authors.lastname: Hastie
authors.forename: M
authors.initials: M
authors.lastname: Bruce
authors.forename: I J
authors.initials: IJ
authors.lastname: Jackson
mesh_terms: D000367:Age Factors; D000483:Alleles; D000818:Animals; D002417:Cattle; D003433:Crosses, Genetic; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics* / Q000503:physiopathology*; D004777:Environment; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011328:Prions / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D011328:Prions