Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.
Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.
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DOI：
10.1371/journal.pone.0109737
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sakaguchi S
中科院分区：
文献类型：
--
作者：
Uchiyama K;Miyata H;Yano M;Yamaguchi Y;Imamura M;Muramatsu N;Das NR;Chida J;Hara H;Sakaguchi S
在朊病毒疾病中，朊病毒感染诱导正常朊病毒蛋白PrPC构象转化为致病性同种型PrPSc。研究表明，PrP敲除（Prnp 0/0）小鼠用缺乏N-末端残基23-88的小鼠-仓鼠嵌合PrP转基因重建，或Tg（MHM 2 Δ23-88）/Prnp 0/0小鼠，在接种RML朊病毒后，既未发生疾病，也未在其脑中积累MHM 2Sc Δ23-88。相比之下，RML接种的Tg（MHM 2 Δ23-88）/Prnp 0/+小鼠发展为在其脑中具有丰富的MHM 2Sc Δ23-88积累的疾病。这些结果表明，MHM 2 Δ23-88本身可能失去或大大降低转化为MHM 2Sc Δ23-88的能力，并且共表达野生型PrPC可以刺激MHM 2 Δ23-88转化为MHM 2Sc Δ23-88。我们证实，Tg（MHM 2 Δ23-88）/Prnp 0/0小鼠在接种后对RML朊病毒保持抗性长达730天。然而，我们发现Tg（MHM 2 Δ23-88）/Prnp 0/0小鼠对22 L朊病毒易感，随着潜伏时间的延长和MHM 2Sc Δ23-88在其脑中的积累而发展疾病。我们还发现在RML-和22 L-接种的Tg（MHM 2 Δ23 - 88）/Prnp 0/+小鼠的脑中，MHM 2 Δ 23 - 88加速转化为MHM 2Sc Δ23 -88。然而，与RML-和22 L-接种的Prnp 0/+小鼠相比，野生型PrPSc在这些接种的Tg（MHM 2 Δ23-88）/Prnp 0/+小鼠的脑中积累较少。这些结果表明，MHM 2 Δ23-88本身可以在没有反式作用PrPC的帮助下转化为MHM 2Sc Δ23-88，并且无论接种的朊病毒菌株如何，共表达野生型PrPC都刺激MHM 2 Δ23-88转化为MHM 2Sc Δ23-88，但相反，共表达MHM 2 Δ23-88干扰野生型PrPC转化为PrPSc。
Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice, compared with RML- and 22L-inoculated Prnp0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.
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影响因子：
16.6
作者：
Goold, R.;Rabbanian, S.;Sutton, L.;Andre, R.;Arora, P.;Moonga, J.;Clarke, A. R.;Schiavo, G.;Jat, P.;Collinge, J.;Tabrizi, S. J.
通讯作者：
Tabrizi, S. J.
影响因子：
6.7
作者：
Miller, Michael B.;Geoghegan, James C.;Supattapone, Surachai
通讯作者：
Supattapone, Surachai
影响因子：
16.6
作者：
Caughey B;Baron GS;Chesebro B;Jeffrey M
通讯作者：
Jeffrey M
DOI：
10.1073/pnas.94.19.10086
发表时间：
1997-09-16
影响因子：
11.1
作者：
James, TL;Liu, H;Cohen, FE
通讯作者：
Cohen, FE
DOI：
10.1073/pnas.94.25.13452
发表时间：
1997-12-09
影响因子：
11.1
作者：
Donne, DG;Viles, JH;Dyson, HJ
通讯作者：
Dyson, HJ