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The glycosylation status of PrPC is a key factor in determining transmissible spongiform encephalopathy transmission between species.

Wiseman FK, Cancellotti E, Piccardo P, Iremonger K, Boyle A, Brown D, Ironside JW, Manson JC, Diack AB - J. Virol. (2015)

Bottom Line: The absence of glycosylation at both or the first PrP(C) glycosylation site in the host results in almost complete resistance to disease.We infected mice that express different forms of glycosylated PrP(C) with three different TSE agents.We demonstrate that changing the glycosylation status of the host can have profound effects on disease transmission, changing host susceptibility and incubation times.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, United Kingdom.

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Lesion profile analysis of wild-type (Wt) and G2 mice after intracerebral inoculation with sCJDMM2 (A), second passage of sCJDMM2 (B), vCJD (C), and second passage of vCJD (D). The second passage was carried out from selected G2 and wild-type mice showing TSE vacuolation and/or PrP. Group size, n ≥ 6 (± standard errors of the means). Gray matter scoring regions are labeled G1 to G9: G1, dorsal medulla; G2, cerebellar cortex; G3, superior colliculus; G4, hypothalamus; G5, thalamus; G6, hippocampus; G7, septum; G8, retrosplenial cortex; G9, cingulate and adjacent motor cortex. White-matter scoring regions are labeled W1 to W3: W1, cerebellar white matter; W2, mesencephalic tegmentum; W3, pyramidal tract.
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Figure 1: Lesion profile analysis of wild-type (Wt) and G2 mice after intracerebral inoculation with sCJDMM2 (A), second passage of sCJDMM2 (B), vCJD (C), and second passage of vCJD (D). The second passage was carried out from selected G2 and wild-type mice showing TSE vacuolation and/or PrP. Group size, n ≥ 6 (± standard errors of the means). Gray matter scoring regions are labeled G1 to G9: G1, dorsal medulla; G2, cerebellar cortex; G3, superior colliculus; G4, hypothalamus; G5, thalamus; G6, hippocampus; G7, septum; G8, retrosplenial cortex; G9, cingulate and adjacent motor cortex. White-matter scoring regions are labeled W1 to W3: W1, cerebellar white matter; W2, mesencephalic tegmentum; W3, pyramidal tract.

Mentions: G2 transgenic mice were susceptible to sCJDMM2, in contrast to the G1, G3, and wild-type mice (Table 1; also see Fig. 2D). Seven out of 20 of the sCJDMM2-challenged G2 transgenic mice developed clinical disease with an average incubation time of 404 ± 8 days (Table 1). Disease status was confirmed by pathology within the brain in which both TSE vacuolation and PrP deposition were observed (Fig. 1A and 2A). PK-resistant PrPSc also was detected by Western blotting in brains of these mice (Fig. 3A). The molecular weight of PrPSc in these samples is consistent with the majority of PrPSc being monoglycosylated, as observed in previous studies using these mice (23). Thus, removal of the second glycosylation site of the host PrPC has rendered the host susceptible to cross-species transmission with sCJDMM2.


The glycosylation status of PrPC is a key factor in determining transmissible spongiform encephalopathy transmission between species.

Wiseman FK, Cancellotti E, Piccardo P, Iremonger K, Boyle A, Brown D, Ironside JW, Manson JC, Diack AB - J. Virol. (2015)

Lesion profile analysis of wild-type (Wt) and G2 mice after intracerebral inoculation with sCJDMM2 (A), second passage of sCJDMM2 (B), vCJD (C), and second passage of vCJD (D). The second passage was carried out from selected G2 and wild-type mice showing TSE vacuolation and/or PrP. Group size, n ≥ 6 (± standard errors of the means). Gray matter scoring regions are labeled G1 to G9: G1, dorsal medulla; G2, cerebellar cortex; G3, superior colliculus; G4, hypothalamus; G5, thalamus; G6, hippocampus; G7, septum; G8, retrosplenial cortex; G9, cingulate and adjacent motor cortex. White-matter scoring regions are labeled W1 to W3: W1, cerebellar white matter; W2, mesencephalic tegmentum; W3, pyramidal tract.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4403468&req=5

Figure 1: Lesion profile analysis of wild-type (Wt) and G2 mice after intracerebral inoculation with sCJDMM2 (A), second passage of sCJDMM2 (B), vCJD (C), and second passage of vCJD (D). The second passage was carried out from selected G2 and wild-type mice showing TSE vacuolation and/or PrP. Group size, n ≥ 6 (± standard errors of the means). Gray matter scoring regions are labeled G1 to G9: G1, dorsal medulla; G2, cerebellar cortex; G3, superior colliculus; G4, hypothalamus; G5, thalamus; G6, hippocampus; G7, septum; G8, retrosplenial cortex; G9, cingulate and adjacent motor cortex. White-matter scoring regions are labeled W1 to W3: W1, cerebellar white matter; W2, mesencephalic tegmentum; W3, pyramidal tract.
Mentions: G2 transgenic mice were susceptible to sCJDMM2, in contrast to the G1, G3, and wild-type mice (Table 1; also see Fig. 2D). Seven out of 20 of the sCJDMM2-challenged G2 transgenic mice developed clinical disease with an average incubation time of 404 ± 8 days (Table 1). Disease status was confirmed by pathology within the brain in which both TSE vacuolation and PrP deposition were observed (Fig. 1A and 2A). PK-resistant PrPSc also was detected by Western blotting in brains of these mice (Fig. 3A). The molecular weight of PrPSc in these samples is consistent with the majority of PrPSc being monoglycosylated, as observed in previous studies using these mice (23). Thus, removal of the second glycosylation site of the host PrPC has rendered the host susceptible to cross-species transmission with sCJDMM2.

Bottom Line: The absence of glycosylation at both or the first PrP(C) glycosylation site in the host results in almost complete resistance to disease.We infected mice that express different forms of glycosylated PrP(C) with three different TSE agents.We demonstrate that changing the glycosylation status of the host can have profound effects on disease transmission, changing host susceptibility and incubation times.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, United Kingdom.

Show MeSH
Related in: MedlinePlus