Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice
Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice
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DOI：
10.1046/j.1471-4159.2003.01916.x
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发表时间：
2003-09-01
影响因子：
4.7
通讯作者：
Hirsch, EC
中科院分区：
文献类型：
--
作者：
Gourfinkel-An, I;Parain, K;Hirsch, EC
亨廷顿氏病是一种常染色体显性遗传病，伴有中等大小纹状体神经元变性。随着疾病的发展，其他神经元群也逐渐受到影响。已经开发出一种表达人类亨廷顿基因外显子1的转基因小鼠模型（R6/2），该模型具有大约150个GAG重复序列，但据报道，这些动物纹状体中的GABA浓度正常。本研究采用谷氨酸脱羧酶（GAD）67 mRNA原位杂交的方法，分析了R6/2转基因小鼠和野生型仔鼠脑gaba能系统的状态。我们发现GAD（67）在R6/2小鼠的纹状体、小脑和中隔中表达正常，而在额叶皮层、顶叶皮层、苍白球、束内核和网状黑质中表达降低。这些数据可能在一定程度上解释了这些动物的行为变化，它们表明，在12.5周龄时，这些小鼠的病理特征与患有亨廷顿舞蹈症的人类不同。
Huntington's disease is an autosomal dominant disorder with degeneration of medium size striatal neurones. As the disease evolves, other neuronal populations are also progressively affected. A transgenic mouse model of the disease (R6/2) that expresses exon 1 of the human Huntington gene with approximately 150 GAG repeats has been developed, but GABA concentrations are reported to be normal in the striatum of these animals. In the present study, we analysed the status of GABAergic systems by means of glutamic acid decarboxylase (GAD)67 mRNA in situ hybridization in the brain of R6/2 transgenic mice and wild-type littermates. We show that GAD(67) expression is normal in the striatum, cerebellum and septum but decreased in the frontal cortex, parietal cortex, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata of R6/2 mice. These data, which may, in part, account for the behavioural changes seen in these animals, indicate that at 12.5 weeks of age the pathological features seen in the mice differ from those seen in humans with Huntington's disease.