title: Sex effects in mouse prion disease incubation time.
abstract: Prion disease incubation time in mice is determined by many factors including PrP expression level, Prnp alleles, genetic background, prion strain and route of inoculation. Sex differences have been described in age of onset for vCJD and in disease duration for both vCJD and sporadic CJD and have also been shown in experimental models. The sex effects reported for mouse incubation times are often contradictory and detail only one strain of mice or prions, resulting in broad generalisations and a confusing picture. To clarify the effect of sex on prion disease incubation time in mice we have compared male and female transmission data from twelve different inbred lines of mice inoculated with at least two prion strains, representing both mouse-adapted scrapie and BSE. Our data show that sex can have a highly significant difference on incubation time. However, this is limited to particular mouse and prion strain combinations. No sex differences were seen in endogenous PrP(C) levels nor in the neuropathological markers of prion disease: PrP(Sc) distribution, spongiosis, neuronal loss and gliosis. These data suggest that when comparing incubation times between experimental groups, such as testing the effects of modifier genes or therapeutics, single sex groups should be used.
authors.affiliation: Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, London, United Kingdom.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Akhtar
authors.forename: Adam
authors.initials: A
authors.lastname: Wenborn
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D007178:Inbreeding; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology*; D012727:Sex Characteristics; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D018620:PrPSc Proteins