【摘要】 Pink 1基因编码定位于线粒体上的丝/苏氨酸激酶(即PARK6),为常染色体隐性遗传性帕金森病(Parkinson’s disease,PD)连锁的基因.该基因在遗传性和散发性PD的发病中起重要作用,但其发病机理尚未明确.本研究以近交系C57BL/6J(B6)和DBA/2J(D2)小鼠制作MPTP诱导的PD鼠为模型,借助基因表达数量性状基因座(eQTL),结合分子生物学方法,分析Pink1的表达调控.结果显示,Pink 1基因在PD模型组中表达显著升高.区间连锁分析检测显示,引起Pink 1基因表达水平差异的染色体区域,定位于4号染色体上,距Pink 1基因自身5 Mb范围之类,属于顺式调节eQTL.Pearson相关分析表明,在BXD基因重组近交系(recombinant inbred,RI)小鼠脑中,Camk2n等30个基因的表达与Pink 1基因高度相关,相互间可能存在一定的协同作用.Pink 1基因在行使特定生物学功能时,很可能协同这些基因一起发挥相应的作用,这部分基因是深入研究Pink 1基因在PD发病中分子机制的重要靶点.更多还原

【Abstract】 PTEN-induced putative kinase 1(Pink 1) is a mitochondrial serine/threonine-protein kinase encoded by the Pink1(PARK6) gene.Mutations in this gene cause an autosomal recessive form of Parkinson’s disease(PD),which plays an important role in pathogenesis of genetic and sporadic PD.But little was known about its expression mechanism.We make MPTP-induced PD model using inbred mouse strains C57BL/6J(B6) and DBA/2J(D2) to investigate the regulatory mechanism of Pink1 gene.Interval linkage analysis showed that Pink 1 eQTL was located in chromosome 4,which could be a cis-regulated eQTL(cis-eQTL),suggesting a kind of cis-regulatory mechanism in Pink 1 gene expression variation.Pearson correlation analysis between Pink 1 and the transcription of the whole mouse genome showed that the expressions of 30 genes such as Camk2n are highly correlated with the Pink 1 gene in the BXD RI mouse,elucidating a cooperative interaction between these genes.These high correlated genes could have a synergistic effect of Pink 1 and could be important targets of the study of Pink 1 in pathologies of PD.更多还原