Naef R, Adlkofer K, Lescher B, Suter U
Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland.
Mol Cell Neurosci. 1997 Jan;9(1):13-25. doi: 10.1006/mcne.1997.0604.
The naturally occurring mouse mutant Trembler (Tr) represents an animal model for inherited human neuropathies caused by point mutations affecting peripheral myelin protein 22 (PMP22). We describe the likely pathogenic cellular mechanism underlying the observed myelin deficiency. In Tr/+ animals, PMP22 immunoreactivity was found not only in compact myelin but also abundantly in the cytoplasm of Schwann cells. Based on these observations, the biosynthesis of wildtype and Tr protein was examined in transfected cells. While wildtype PMP22 was readily transported to the plasma membrane, Tr protein was localized mainly in the endoplasmic reticulum. Coexpression revealed a dominant effect of Tr on protein trafficking of wildtype PMP22. In agreement with the findings in vitro, Tr protein was not detectable in myelin of Tr/0 mice.
天然存在的小鼠突变体震颤鼠（Tr）代表了一种由影响外周髓磷脂蛋白22（PMP22）的点突变引起的遗传性人类神经病变的动物模型。我们描述了观察到的髓磷脂缺乏背后可能的致病细胞机制。在Tr/+动物中，不仅在致密髓磷脂中发现了PMP22免疫反应性，而且在施万细胞的细胞质中也大量存在。基于这些观察结果，在转染细胞中检测了野生型和Tr蛋白的生物合成。虽然野生型PMP22很容易转运到质膜，但Tr蛋白主要定位于内质网。共表达揭示了Tr对野生型PMP22蛋白转运的显性作用。与体外研究结果一致，在Tr/0小鼠的髓磷脂中未检测到Tr蛋白。
