Reassessment of corticospinal tract regeneration in Nogo-deficient mice.
Reassessment of corticospinal tract regeneration in Nogo-deficient mice.
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DOI：
10.1523/jneurosci.1864-09.2009
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发表时间：
2009-07-08
期刊：
影响因子：
--
通讯作者：
Zheng B
中科院分区：
文献类型：
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作者：
Lee JK;Chan AF;Luu SM;Zhu Y;Ho C;Tessier-Lavigne M;Zheng B
髓鞘来源的轴突生长抑制剂Nogo被认为在阻止中枢神经系统(CNS)损伤后轴突再生方面发挥了重要作用。然而，过去的研究对各种Nogo缺陷小鼠在实验性脊髓损伤后的再生表型产生了不同的结果。2例未见皮质脊髓束(CST)增强再生，1例轻度再生。第四个品系，一个Nogo-A，B基因陷阱突变体，据报道显示了广泛的CST再生，但后来发现结果无意中与轴突标记制品混淆了。到目前为止，在所研究的四个Nogo突变系中，有三个继续表达某种形式的Nogo(S)，这使得是否有剩余的Nogo蛋白对某些报道的适度再生表型有贡献的问题悬而未决。被研究的其余Nogo突变系被与该突变相关的胚胎致死的不明原因的拯救所混淆。为了更好地了解Nogo作为中枢神经系统轴突尤其是CST轴突再生抑制因子的作用，我们重新分析了Nogo-A、B基因陷阱突变系，并分析了一个新的、完全可行的Nogo缺失突变系，该突变系在所有已知的Nogo亚型中都为零。我们的分析未能显示在任何一条线的实验性脊髓损伤后有任何增强的CST再生。这些结果表明，Nogo本身并不能解释CST再生的缺乏，并且通过靶向Nogo对目前人类脊髓损伤的治疗发展有一定的意义。
The myelin-derived neurite growth inhibitor Nogo has been proposed to play a major role in blocking axon regeneration in the central nervous system (CNS) after injuries. However, past studies have produced mixed results regarding the regenerative phenotype of various Nogo deficient mouse lines after experimental spinal cord injury. Two lines did not display enhanced corticospinal tract (CST) regeneration, and one displayed modest regeneration. A fourth line, a Nogo-A,B gene trap mutant, was instead reported to exhibit extensive CST regeneration but the results were later found to be inadvertently confounded with an axon labeling artifact. Of the four Nogo mutant lines studied so far, three continue to express some isoform(s) of Nogo, leaving open the question whether any remaining Nogo protein contributes to the modest regenerative phenotype reported in some. The remaining Nogo mutant line studied was confounded by the unexplained rescue of embryonic lethality associated with this mutation. In order to gain a better understanding of the contribution of Nogo as an inhibitor of regeneration of CNS axons, and particularly CST axons, we re-analyzed the Nogo-A,B gene-trap mutant line and analyzed a novel, fully viable Nogo deletion mutant line that is null for all known isoforms of Nogo. Our analyses failed to reveal any enhanced CST regeneration after experimental spinal cord injury in either line. These results indicate that Nogo alone does not account for lack of CST regeneration, and have implications for current therapeutic development for spinal cord injury in humans by targeting Nogo.