Wlds mice are resistant to paclitaxel (Taxol) neuropathy
Wlds mice are resistant to paclitaxel (Taxol) neuropathy
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DOI：
10.1002/ana.10300
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发表时间：
2002-10-01
影响因子：
11.2
通讯作者：
Glass, JD
中科院分区：
文献类型：
--
作者：
Wang, MS;Davis, AA;Glass, JD
Wld（S）小鼠是一种独特的突变品系，其表现出横切轴突存活延长的显著表型（“缓慢沃勒变性”）。在这些研究中，我们测试了这种神经保护表型是否延伸到在进行性周围神经病变中观察到的轴突变性。将Wld（S）和野生型小鼠用癌症化疗剂紫杉醇（Taxol）中毒。结果感觉神经病变的严重程度与行为，生理和病理措施进行了比较。Wld（S）小鼠对紫杉醇神经病变的所有措施都有抵抗力，这种抵抗力是因为对轴突变性的保护。这些研究首次证明，Wld（S）小鼠不仅仅是一种缓慢的沃勒变性表型，强调了沃勒变性和周围神经病变之间的机制联系。了解这种突变基因如何赋予对轴突变性的保护将为预防几种人类神经系统疾病的轴突变性提供重要线索。
The Wld(S) mouse is a unique mutant strain that demonstrates the remarkable phenotype of prolonged survival of transected axons ("slow Wallerian degeneration"). In these studies, we tested whether this neuroprotective phenotype extends to axonal degeneration seen in a progressive peripheral neuropathy. Wld(S) and wild-type mice were intoxicated with the cancer chemotherapeutic agent paclitaxel (Taxol). The severity of the resultant sensory neuropathy was compared with behavioral, physiological, and pathological measures. Wld(S) mice were resistant to paclitaxel neuropathy by all measures, and the resistance was because of protection against axonal degeneration. These studies demonstrate for the first time that the Wld(S) mouse is more than a slow Wallerian degeneration phenotype, emphasizing the mechanistic link between Wallerian degeneration and peripheral neuropathy. Understanding how this mutant gene confers protection against axonal degeneration will provide important clues toward prevention of axonal degeneration in several human neurological disorders.