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 PrPC levels nor in the neuropathological markers of prion disease: PrPSc 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.
Highlights
Prion diseases or transmissible spongiform encephalopathies involve the conversion of the normal host PrPC to an abnormal form, PrPSc
Sex effects have been implicated in prion disease incubation time for many years, to date, these data have been equivocal with few conclusions drawn
We have presented a comprehensive study with 12 different inbred lines of mice all of which were challenged with a mouse-adapted scrapie strain of prions (Chandler/RML) and mouse-adapted bovine spongiform encephalopathy (BSE) (I874)
Summary
Prion diseases or transmissible spongiform encephalopathies involve the conversion of the normal host PrPC to an abnormal form, PrPSc. Human prion diseases have three distinct aetiologies: sporadic, inherited and acquired. Sporadic CJD is the most common form of human prion disease accounting for ,85% of all cases and to date there is no known cause. 15% of cases are inherited or familial and are caused by mutations in the prion gene (PRNP). Prion diseases are infectious and are transmissible (acquired). Human prion diseases have been transmitted through medical procedures (iatrogenic) such as the administration of contaminated pituitary hormones and the use of infected neurosurgical electrodes. Following human exposure to BSE contaminated material, a new acquired prion disease, variant CJD (vCJD), was recognised
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
