A novel system to accelerate the progression of nerve degeneration in transgenic mouse models of neuropathies.
A novel system to accelerate the progression of nerve degeneration in transgenic mouse models of neuropathies.
复制标题
DOI：
10.1016/j.expneurol.2012.05.021
复制
发表时间：
2012-09
影响因子：
5.3
通讯作者：
Thien Nguyen
中科院分区：
文献类型：
--
作者：
Ewaleifoh, Osefame;Minh Trinh;Griffin, John W.;Thien Nguyen
轴突变性是许多神经退行性疾病的共同特征。现在有大量的自发和基因工程小鼠可用于研究轴突变性的机制和筛选轴突保护剂。然而，这些小鼠模型中的许多都表现出缓慢的进行性轴突丢失，可能持续数月。因此，迫切需要在短时间内加快轴突丢失的速度，以便高通量筛选药物和遗传疗法。在这里，我们提出了一种新的技术，使用丙烯酰胺，一种轴突神经毒素，在神经病的小鼠模型中引发快速轴突变性。进行性轴突丢失通常发生在8个月以上，在丙烯酰胺中毒后7-10天内复制。该方法被成功地应用于髓鞘相关糖蛋白基因敲除(MAG−/−)小鼠和颤抖者-J小鼠(一种流行的夏科-玛丽-牙病1型小鼠模型)。转基因小鼠的丙烯酰胺中毒提供了一种新的实验方法，可以在短时间内加速轴突丢失的速度，为及时进行神经变性的体内研究提供了一种新的实验方法。这份报告还首次提供了药物或毒素诱导的先前存在的神经病恶化的动物模型，这种现象在神经病患者中被广泛报道。
Axon degeneration is a common hallmark of many neurodegenerative diseases. There is now an abundance of spontaneous and genetically engineered mice available to study the mechanisms of axonal degeneration and to screen for axonal protective agents. However, many of these mouse models exhibit slow progressive axonal loss which can span over many months. Consequently, there is a pressing need to accelerate the pace of axonal loss over a short interval for high-throughput screening of pharmacological and genetic therapies. Here, we present a novel technique using acrylamide, an axonal neurotoxin, to provoke rapid axonal degeneration in murine models of neuropathies. The progressive axonal loss which typically occurs over 8 months was reproduced within 7 to 10 days of the acrylamide intoxication. This approach was successfully applied to Myelin Associated Glycoprotein knockout (MAG−/−) mouse and Trembler-J mouse, a popular murine model of Charcot-Marie-Tooth disease type 1 (CMT-1). Acrylamide intoxication in transgenic mouse models offers a novel experimental approach to accelerate the rate of axonal loss over short intervals for timely in vivo studies of nerve degeneration. This report also provides for the first time an animal model for medication or toxin induced exacerbation of pre-existing neuropathies, a phenomenon widely reported in patients with neuropathies.
登录
查看更多内容
影响因子：
5.3
作者：
Pan, BH;Fromholt, SE;Schnaar, RL
通讯作者：
Schnaar, RL
影响因子：
5.3
作者：
Yin, XH;Crawford, TO;Trapp, BD
通讯作者：
Trapp, BD
DOI：
10.1002/neu.480080407
发表时间：
1977-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
GRIFFIN, JW;PRICE, DL;DRACHMAN, DB
通讯作者：
DRACHMAN, DB
影响因子：
3.8
作者：
Meekins, GD;Emery, MJ;Weiss, MD
通讯作者：
Weiss, MD
影响因子：
1.7
作者：
Ng, WP;Cartel, N;Lozano, A
通讯作者：
Lozano, A