...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Modified adeno-associated virus targets the bacterial enzyme chondroitinase ABC to select mouse neuronal populations in vivo using the Cre-LoxP system
【24h】

Modified adeno-associated virus targets the bacterial enzyme chondroitinase ABC to select mouse neuronal populations in vivo using the Cre-LoxP system

机译：修饰的腺相关病毒针对细菌酶软骨素酶ABC，使用CRE-LOXP系统选择体内小鼠神经元群体

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Current methods of experimentally degrading the specialized extracellular matrix (ECM), perineuronal nets (PNNs) have several limitations. Genetic knockout of ECM components typically has only partial effects on PNNs, and knockout of the major ECM component aggrecan is lethal in mice. Direct injection of the chondroitinase ABC (ChABC) enzyme into the mammalian brain is effective at degrading PNNs in vivo but this method typically lacks consistent, localized spatial targeting of PNN degradation. PNNs also regenerate within weeks after a ChABC injection, thus limiting the ability to perform long-term studies. Previous work has demonstrated that viral delivery of ChABC in mammalian neurons can successfully degrade PNNs for much longer periods, but the effects are similarly diffuse beyond the injection site. In an effort to gain cell-specific targeting of ChABC, we designed an adeno-associated virus encoding ChABC under the control of the Cre-LoxP system. We show that this virus is effective at targeting the synthesis of ChABC to Cre-expressing mouse neurons in vivo. Although ChABC expression is localized to the Cre-expressing neurons, we also note that ChABC is apparently trafficked and secreted at projection sites, as was previously reported for the non-Cre dependent construct. Overall, this method allows for cell-specific targeting of ChABC and long-term degradation of PNNs, which will ultimately serve as an effective tool to study the function of cell-autonomous regulation of PNNs in vivo. This novel approach may also aid in determining whether specific, long-term PNN loss is an appropriate strategy for treatment of neurodevelopmental disorders associated with PNN pathology.
机译：目前实验降解特殊细胞外基质（ECM）和神经周围网（PNN）的方法有几个局限性。ECM组分的基因敲除通常仅对PNN产生部分影响，而主要ECM组分聚集蛋白聚糖的敲除对小鼠是致命的。将软骨素酶ABC（ChABC）酶直接注射到哺乳动物大脑中可有效降解体内的PNN，但这种方法通常缺乏PNN降解的一致、局部空间靶向性。PNN在注射ChABC后数周内也会再生，因此限制了进行长期研究的能力。之前的研究已经证明，在哺乳动物神经元中通过病毒传递ChABC可以成功降解PNN更长的时间，但其作用在注射部位之外也同样扩散。为了获得ChABC的细胞特异性靶向性，我们设计了一种在Cre-LoxP系统控制下编码ChABC的腺相关病毒。我们证明，这种病毒在体内有效地将ChABC合成靶向表达Cre的小鼠神经元。尽管ChABC的表达局限于表达Cre的神经元，但我们也注意到，ChABC显然是在投射位点被运输和分泌的，正如之前报道的非Cre依赖结构。总的来说，这种方法可以实现ChABC的细胞特异性靶向和PNN的长期降解，最终将成为研究体内PNN细胞自主调节功能的有效工具。这种新的方法也可能有助于确定特定的、长期的PNN丢失是否是治疗与PNN病理相关的神经发育障碍的合适策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号