Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an alpha-helix
Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an alpha-helix
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DOI：
10.1038/nm0797-750
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发表时间：
1997-07-01
期刊：
影响因子：
82.9
通讯作者：
Prusiner, SB
中科院分区：
文献类型：
--
作者：
Muramoto, T;DeArmond, SJ;Prusiner, SB
小鼠被构建为携带朊病毒蛋白（PrP）转基因，并删除了推定二级结构的各个区域。删除氨基末端区域的转基因小鼠在> 400天龄时仍保持健康，而删除任何一个羧基末端α螺旋的转基因小鼠会自发地患上类似于神经元贮积病的致命中枢神经系统疾病。任一 C 末端螺旋的缺失都会导致 PrP 在增大的神经元的细胞质内含物内积聚。倒数第二个C末端螺旋的缺失导致粗面内质网增殖。 C末端螺旋被删除的小鼠受到海马神经细胞损失和平滑内质网增殖的影响。是否会发现患有这种人类疾病的儿童仍有待确定。
Mice were constructed carrying prion protein (PrP) transgenes with individual regions of putative secondary structure deleted. Transgenic mice with amino-terminal regions deleted remained healthy at >400 days of age, whereas those with either of carboxy-terminal alpha-helices deleted spontaneously developed fatal CNS illnesses similar to neuronal storage diseases. Deletion of either C-terminal helix resulted in PrP accumulation within cytoplasmic inclusions in enlarged neurons. Deletion of the penultimate C-terminal helix resulted in proliferation of rough endoplasmic reticulum. Mice with the C-terminal helix deleted were affected with nerve cell loss in the hippocampus and proliferation of smooth endoplasmic reticulum. Whether children with the human counterpart of this malady will be found remains to be determined.