A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats
A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats
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DOI：
10.1016/j.nbd.2009.08.002
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发表时间：
2010-02-01
影响因子：
6.1
通讯作者：
Riess, Olaf
中科院分区：
文献类型：
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作者：
Boy, Jana;Schmidt, Thorsten;Riess, Olaf
脊髓小脑性共济失调3型（SCA 3），或马查多-约瑟夫病（MJD），是由共济失调蛋白-3蛋白中多聚谷氨酰胺重复序列的扩增引起的。我们建立了一个SCA 3表达共济失调蛋白-3的小鼠模型，该共济失调蛋白-3在亨廷顿蛋白启动子的控制下具有148个CAG重复序列，导致在整个大脑中无处不在的表达。该模型类似于人类疾病的许多特征，包括症状的迟发性和传播给后代的CAG重复不稳定性。我们观察到一个双相进展的疾病，与多动症在第一个月和下降的运动协调约1岁后，然而，核内聚集在这个年龄是不可见的。少数和小的核内聚集体首次出现在18个月的年龄，进一步支持神经元功能障碍之前的核内聚集体的形成的说法。(c)2009 Elsevier Inc. All rights reserved.
Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is caused by the expansion of a polyglutamine repeat in the ataxin-3 protein. We generated a mouse model of SCA3 expressing ataxin-3 with 148 CAG repeats under the control of the huntingtin promoter, resulting in ubiquitous expression throughout the whole brain. The model resembles many features of the disease in humans, including a late onset of symptoms and CAG repeat instability in transmission to offspring. We observed a biphasic progression of the disease, with hyperactivity during the first months and decline of motor coordination after about 1 year of age; however, intranuclear aggregates were not visible at this age. Few and small intranuclear aggregates appeared first at the age of 18 months, further supporting the claim that neuronal dysfunction precedes the formation of intranuclear aggregates. (c) 2009 Elsevier Inc. All rights reserved.