Analysis of linkage between scrapie incubation period and the prion protein gene in mice

Race, Richard E.; Graham, Kenneth; Ernst, Darwin; Caughey, Byron; Chesebro, Bruce

doi:10.1099/0022-1317-71-2-493

Cited by 69 publications

(34 citation statements)

References 19 publications

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“…In linkage studies in other laboratories, a few possible individual recombinants have been identified in crosses between non-congenic mouse strains in which incubation period and PrP did not segregate together (Carlson et al, 1988;Race et al, 1990). However, there is doubt as to whether these really were recombinants, firstly because of possible effects of genes other than Sinc on incubation period in these non-congenic strains.…”

Section: Discussionmentioning

confidence: 99%

The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis

Bruce

McConnell

Fraser

et al. 1991

Journal of General Virology

363

248

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Mouse lines which are congenic for Sinc, the major gene controlling scrapie incubation period, have been produced by selective breeding from the inbred C57BL (Sinc sT) and VM (Sinc p7) strains; the s7 allele of Sinc has been introduced into a VM background by 18 serial backcrosses, at each generation selecting on the basis of the incubation period with the ME7 scrapie strain. The characteristics of the disease produced by seven scrapie strains have been compared in Sinc ~7 and Sinc p7 congenic mice and in the F1 cross between them. As previously found in non-congenic mice, each scrapie strain has a characteristic, precisely reproducible incubation period pattern in the three Sinc genotypes. The Sinc gene controls the incubation period for all scrapie strains tested but the direction of allelic action and the apparent dominance pattern differs between scrapie strains. Comparison with non-congenic mice shows that other genes also have a minor effect on incubation period. The distribution of vacuolar degeneration in the brain depends mainly on the scrapie strain but is also influenced by Sinc and other unspecified mouse genes. Restriction fragment length polymorphism analysis has already shown that the close linkage between Sinc and the gene encoding PrP has been maintained in the Sinc congenic lines, strengthening the possibility that PrP is the Sinc gene product. The present study confirms that scrapie strains carry information which is independent of the host but nevertheless suggests that host PrP protein interacts with this information to regulate the progression of the disease.

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Section: Discussionmentioning

confidence: 99%

The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis

Bruce

McConnell

Fraser

et al. 1991

Journal of General Virology

363

248

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“…Genetic studies in mice revealed a single gene that markedly altered scrapie incubation times (4). Subsequent molecular genetic studies showed that the scrapie incubation-time gene is linked to or identical with the prion protein (PrP) gene (5)(6)(7)(8).…”

mentioning

confidence: 99%

Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform.

DeArmond

Yang

Lee

et al. 1993

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

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To investigate the molecular basis of prion diversity, we inoculated transgenic mice expressing the Syrian hamster prion protein (PrP) with three distinct prion isolates. We compared the three isolates designated Sc237, 139H, and Me7H in Tg(SHaPrP)7 mice with clinical signs of scrapie because the incubation times with these mice are considerably shorter than the times found with hamsters. Each prion isolate produced a distinctive pattern of the scrapie isoform of PrP (PrPsc) accumulation, as determined by histoblotting, a technique developed for the regional mapping of PrPsc deposition.The PrPsc pattern with the Me7H isolate was particularly interesting because it appeared to be confined to the hypothalamus and related structures-including the interstitial nucleus of the stria terminalis, the paraventricular nucleus of the thalamus, and periaqueductal grey. Additionally, the regions of PrPsc accumulation remained highly restricted, even though the incubation time for Me7H scrapie was significantiy longer than with Sc237 and 139H isolates. Neuropathological changes characterized by neuronal vacuolation and astrocytic gliosis were confined to those regions where PrPsc accumulated. These findings argue that the cell-speciffc propagation of prion isolates may be responsible for different properties exhibited by each of the isolates.

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“…Distinct isolates of the scrapie agent have often been referred to as strains. Although earlier studies were complicated by the use of Prn-p a and Prn-p b mice (Carlson et al 1986(Carlson et al , 1988Hunter et al 1987;Westaway et al 1987Westaway et al , 1991Race et al 1990), the existence of at least a few scrapie isolates in mice seems secure (Bruce and Dickinson 1987;Bruce et al 1991). Derivation of new isolates in Syrian hamsters after passage from mice has also been reported (Kimberlin and Walker 1978;Kimberlin et al 1987bKimberlin et al , 1989.…”

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confidence: 99%

Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.

Hecker¹,

Taraboulos²,

Scott³

et al. 1992

Genes Dev.

206

148

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Studies with transgenic mice expressing foreign and mutant prion protein (PrP) genes have provided a wealth of new knowledge about the structure of the prion particle, the pathogenesis of prion diseases, and the events that feature in the replication of prions (Scott et al. 1989;Hsiao et al. 1990;Prusiner et al. 1990;Westaway et al. 1991). Investigations of transgenic (Syrian hamster PrP) [Tg(SHaPrP)] mice expressing SHaPrP demonstrated that PrP sc in the inoculum dictates whether mouse prions (Mo prions) or Syrian hamster prions (SHa prions) will be produced. Furthermore, the scrapie incubation times and neuropathology are determined by the particular prion synthesized. Although no physical evidence is available, it seems likely that PrP c and PrP sc transiently form a complex during the synthesis of nascent PrP sc molecules Prusiner 1991).Early studies of Dickinson and colleagues not only identified inbred strains of mice with short or long incubation times, but also distinct isolates of the scrapie agent distinguishable by their different incubation times and neuropathologic lesions Dickinson 1968, 1973; Dickinson and Meikle 4present address:

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Analysis of linkage between scrapie incubation period and the prion protein gene in mice

Cited by 69 publications

References 19 publications

The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis

The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis

Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform.

Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.

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