Identification of a gene which controls the incubation period of some strains of scrapie agent in mice

Dickinson, A. G.; Meikle, Veronica M. H.; Fraser, H.

doi:10.1016/0021-9975(68)90005-4

Cited by 406 publications

(193 citation statements)

References 3 publications

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“…Mice were anaesthetized by halothane inhalation and injected intracerebrally with 0.02 ml of inoculum at 3 to 8 weeks of age. All animals were housed under SPF conditions, monitored daily for signs of intercurrent illness, and, from 250 days after BSE challenge, were subject to a formal clinical monitoring system (19). Animals then were checked daily and scored weekly by an experienced observer for clinical signs of TSE-like disease, using well established criteria that have previously been shown to give precise and reproducible measurements of incubation period in an extensive range of TSE studies.…”

Section: Methodsmentioning

confidence: 99%

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

Manolakou

Beaton

McConnell

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

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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 crossspecies 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.

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Section: Methodsmentioning

confidence: 99%

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

Manolakou

Beaton

McConnell

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

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“…Genetic studies of scrapie infection have identified two genes, the Sip and Sinc genes, which have a major influence on the duration of the incubation period (Dickinson et al 1968;Hunter et al 1992;Bruce et al 1994;Farquhar et al 1994). Experimental studies of scrapie have also indicated that some host genotypes appear to be resistant to infection (Davies & Kimberlin 1985;Foster & Dickinson 1988).…”

Section: (D ) Incubation Periodmentioning

confidence: 99%

The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological processes, demography of cattle and approaches to control by culling

Donnelly

Ferguson

Ghani

et al. 1997

Phil. Trans. R. Soc. Lond. B

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This paper explores the key epidemiological processes and demographic factors that determined the pattern of transmission of the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle herds in Great Britain (GB). The analyses presented utilize data from published and unpublished experimental studies and from the GB central database of confirmed BSE cases. We review the experimental and epidemiological evidence that has both confirmed indirect horizontal transmission via the consumption of infectious material as the major transmission route and provided information on the duration and variability of the dose–dependent incubation period of BSE in cattle. The epidemiological and genetic data pertaining to the possible existence of maternal transmission and/or genetically variable susceptibility to infection is discussed. The demography of British cattle is characterized and the impacts of key demographic features on the observed epidemic profile are discussed. In the main BSE case database, analyses reveal that BSE cases cluster significantly at both the holding and county scale. Furthermore, analysis of longitudinal patterns reveal substantial temporal within–holding correlation. Such clustering of cases suggests a highly heterogeneous infection process. The paper ends with a discussion of how analyses of spatio–temporal clustering inform the design of targeted culling programmes aimed at reducing future disease incidence. We show how the retrospective implementation of culling policies on the BSE case database allows the qualitative evaluation of policy performance, but that model predictions of future trends in case incidence are required to estimate the precise impact of any current or future programme.

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“…Three genes that influence the incubation period have been identified. First, Dickinson et al (1968) identified a single autosomal gene designated Sinc (scrapie incubation) and postulated the existence of two alleles only. Subsequently, VM mice were found to possess the prolonged incubation allele p7 and other strains such as C57BL/6 mice had the short incubation s7 allele.…”

Section: Introductionmentioning

confidence: 99%

Host Genetic Control of Incubation Periods of Creutzfeldt-Jakob Disease in Mice

Mohri

Tateishi

1989

Journal of General Virology

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SUMMARYHost genetic control of the incubation period of Creutzfeldt-Jakob disease (CJD) was studied using various inbred strains of mice, including B10 congenic strains. Various incubation periods were found in mice injected either intracerebrally or intraperitoneally with the Fukuoka 1 strain of the CJD agent; NZW/Sea and A/JJms had the shortest, and BI0.AKM/OIa and C57BL/6J the longest, incubation periods. Length of the CJD incubation period did not correlate with the genetic markers tested, i.e. the murine major histocompatibility (H-2) complex (which has previously been reported to be linked to a gene influencing CJD incubation period in mice), coat colour or sex genes. In NZW/Sea × C57BL/6J F 1 hybrid mice the CJD incubation periods were similar to that of the parent with the longest incubation period. Incubation periods of the backcross progeny from F1 and NZW/Sea were intermediate between those of the parental mice and had a unimodal distribution pattern. A similar observation was made on the progeny of the A/JJms x C57BL/6J mating. On the other hand, the length of incubation period for the NZW/Sea x B10. AKM/Ola F1 hybrid fell between those for the two parents and the NZW/Sea x A/JJms F~ hybrid had a significantly longer incubation period than those of the two parents. These results suggest that polygenes probably control the length of the CJD incubation period in mice.

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Identification of a gene which controls the incubation period of some strains of scrapie agent in mice

Cited by 406 publications

References 3 publications

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological processes, demography of cattle and approaches to control by culling

Host Genetic Control of Incubation Periods of Creutzfeldt-Jakob Disease in Mice

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