Simón-Sánchez Javier, Herranz-Pérez Vicente, Olucha-Bordonau Francisco, Pérez-Tur Jordi
Unitat de Genètica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València-CSIC, C/Jaume Roig, 11, E46010 València, Spain.
Eur J Neurosci. 2006 Feb;23(3):659-66. doi: 10.1111/j.1460-9568.2006.04616.x.
The leucine-rich repeat kinase 2 (LRRK2) gene was recently found to have multiple mutations that are causative for autosomal dominant inherited Parkinson's disease (PD). Previously, we used Northern blot analysis to show that this gene was expressed in the cerebellum, cerebral cortex, medulla, spinal cord, occipital pole, frontal lobe, temporal lobe and caudate putamen. However, a more comprehensive map of LRRK2 mRNA localization in the central nervous system is still lacking. In this study we have mapped the distribution of the mRNA encoding for LRRK2 using nonradioactive in situ hybridization. We detected a moderate expression of this PD-related gene throughout the adult B2B6 mouse brain. A stronger hybridization signal was observed in deep cerebral cortex layers, superficial cingulate cortex layers, the piriform cortex, hippocampal formation, caudate putamen, substantia nigra, the basolateral and basomedial anterior amygdala nuclei, reticular thalamic nucleus and also in the cerebellar granular cell layer. Given that LRRK2 mRNA is highly enriched in motor systems and also is expressed in other systems, we may conclude that mutations in LRRK2 may affect several motor and nonmotor structures that may play an important role in the development of PD.
富含亮氨酸重复激酶2(LRRK2)基因最近被发现有多个突变,这些突变是常染色体显性遗传性帕金森病(PD)的病因。此前,我们用Northern印迹分析表明该基因在小脑、大脑皮层、延髓、脊髓、枕叶、额叶、颞叶和尾状壳核中表达。然而,LRRK2 mRNA在中枢神经系统中更全面的定位图谱仍然缺乏。在本研究中,我们使用非放射性原位杂交绘制了编码LRRK2的mRNA的分布图。我们在整个成年B2B6小鼠大脑中检测到了这个与PD相关基因的适度表达。在大脑皮层深层、扣带回皮层浅层、梨状皮层、海马结构、尾状壳核、黑质、杏仁核基底外侧和基底内侧前核、丘脑网状核以及小脑颗粒细胞层观察到更强的杂交信号。鉴于LRRK2 mRNA在运动系统中高度富集且也在其他系统中表达,我们可以得出结论,LRRK2中的突变可能影响几个运动和非运动结构,这些结构可能在PD的发展中起重要作用。