Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain
Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain
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DOI：
10.1093/emboj/20.4.694
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发表时间：
2001-02-15
期刊：
影响因子：
11.4
通讯作者：
Weissmann, C
中科院分区：
文献类型：
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作者：
Rossi, D;Cozzio, A;Weissmann, C
只有开放阅读框被破坏的PrP敲除小鼠（“Zurich I”）保持健康。然而，更广泛的缺失导致共济失调、浦肯野细胞丢失和Doppel（Dpl）在脑中的异位表达，Dpl由下游基因Prnd编码。一个新的PrP基因敲除株Zurich Ⅱ，其Prnp基因缺失2.9kb，在10个月时出现这种表型（发病率50%），一个Prnp等位基因消除了这种综合征。化合物苏黎世I/苏黎世II杂合子的Dpl为苏黎世II小鼠的一半，并在6个月后出现症状。含有Prnd的粘粒转基因的苏黎世II小鼠表达的Dpl水平是5个月前的两倍，并且变得类似于5个月前的共济失调。因此，脑中的Dpl水平与共济失调综合征的发作呈负相关。
PrP knockout mice in which only the open reading frame was disrupted ('Zurich I') remained healthy. However, more extensive deletions resulted in ataxia, Purkinje cell loss and ectopic expression in brain of Doppel (Dpl), encoded by the downstream gene, Prnd. A new PrP knockout line,'Zurich II', with a 2.9 kb Prnp deletion, developed this phenotype at similar to 10 months (50% morbidity), A single Prnp allele abolished the syndrome. Compound Zurich I/Zurich II heterozygotes had half the Dpl of Zurich II mice and developed symptoms 6 months later. Zurich II mice transgenic for a Prnd-containing cosmid expressed Dpl at twice the level and became ataxic similar to5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.