Distribution of PINK1 and LRRK2 in rat and mouse brain
Distribution of PINK1 and LRRK2 in rat and mouse brain
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DOI：
10.1111/j.1471-4159.2006.03919.x
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发表时间：
2006-08-01
影响因子：
4.7
通讯作者：
Baekelandt, Veerle
中科院分区：
文献类型：
--
作者：
Taymans, Jean-Marc;Van den Haute, Chris;Baekelandt, Veerle
两种激酶，PTEN诱导的激酶1（PINK 1）和富含亮氨酸的重复激酶2（LRRK 2）的突变已被证明与帕金森病的家族形式分离。虽然这两个基因被认为与帕金森病的分子机制有关，但它们在哺乳动物大脑中的精确解剖定位尚不清楚。我们已经绘制了PINK 1和LRRK 2 mRNA的表达在大鼠和小鼠脑通过原位杂交组织化学使用核糖核酸探针。我们发现，这两个基因在整个大脑中广泛表达，与大鼠相比，小鼠的神经解剖学分布相似。PINK 1 mRNA丰度在不同脑区中相当均匀，在皮质、纹状体、丘脑、脑干和小脑中表达。另一方面，LRRK 2在表达水平上显示出强烈的区域差异，在纹状体、皮质和海马中观察到最高水平。LRRK 2在下丘脑、嗅球和黑质中表达较弱。我们使用定量RT-PCR和蛋白质免疫印迹法证实了这两种基因的分布。由于其广泛的表达模式与帕金森病中的局部神经病理学形成对比，PINK 1和LRRK 2的临床突变形式的致病性可能由黑质纹状体特异性机制介导。
Mutations in two kinases, PTEN induced kinase 1 (PINK1) and leucine-rich repeat kinase 2 (LRRK2), have been shown to segregate with familial forms of Parkinson's disease. Although these two genes are expected to be involved in molecular mechanisms relevant to Parkinson's disease, their precise anatomical localization in mammalian brain is unknown. We have mapped the expression of PINK1 and LRRK2 mRNA in the rat and mouse brain via in situ hybridization histochemistry using riboprobes. We found that both genes are broadly expressed throughout the brain with similar neuroanatomical distribution in mouse compared to rat. PINK1 mRNA abundance was rather uniform throughout the different brain regions with expression in cortex, striatum, thalamus, brainstem and cerebellum. LRRK2, on the other hand, showed strong regional differences in expression levels with highest levels seen in the striatum, cortex and hippocampus. Weak LRRK2 expression was seen in the hypothalamus, olfactory bulb and substantia nigra. We confirmed these distributions for both genes using quantitative RT-PCR and for LRRK2 by western immunoblot. As their broad expression patterns contrast with localized neuropathology in Parkinson's disease, the pathogenicity of clinical mutant forms of PINK1 and LRRK2 may be mediated by nigrostriatal-specific mechanisms.