A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses
A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses
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DOI：
10.1111/j.1460-9568.2004.03833.x
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Coleman, MP
中科院分区：
文献类型：
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作者：
Adalbert, R;Gillingwater, TH;Coleman, MP
沃勒变性缓慢的表型Wld(S)可将沃勒变性和轴突病变延迟数周，到目前为止仅在小鼠中进行了研究。大鼠模型具有若干优势。首先，大鼠在模拟某些人类疾病方面比小鼠更好。其次，大鼠体型较大，更便于进行复杂的手术操作。第三，大鼠可为原代培养和生化研究提供更多的组织量。我们培育了在中枢和外周神经系统中表达Ube4b/Nmnat1嵌合基因的转基因Wld(S)大鼠。与Wld(S)小鼠一样，它们的轴突在横断后可存活长达3周，并且至少在1周内仍保持功能。对轴突切断的神经末梢的保护作用比小鼠更强，特别是在一个品系中，95 - 100%的神经肌肉接头在5天后仍保持完整且有功能。此外，大鼠随年龄增长出现的突触表型丧失比小鼠少得多。因此，沃勒变性缓慢的表型可转移到另一个哺乳动物物种，并且在轴突较长的物种中，轴突切断后突触可能得到更有效的保护。
The slow Wallerian degeneration phenotype, Wld(S), which delays Wallerian degeneration and axon pathology for several weeks, has so far been studied only in mice. A rat model would have several advantages. First, rats model some human disorders better than mice. Second, the larger body size of rats facilitates more complex surgical manipulations. Third, rats provide a greater yield of tissue for primary culture and biochemical investigations. We generated transgenic Wld(S) rats expressing the Ube4b/Nmnat1 chimeric gene in the central and peripheral nervous system. As in Wld(S) mice, their axons survive up to 3 weeks after transection and remain functional for at least 1 week. Protection of axotomized nerve terminals is stronger than in mice, particularly in one line, where 95-100% of neuromuscular junctions remained intact and functional after 5 days. Furthermore, the loss of synaptic phenotype with age was much less in rats than in mice. Thus, the slow Wallerian degeneration phenotype can be transferred to another mammalian species and synapses may be more effectively preserved after axotomy in species with longer axons.