【摘要】 目的探讨Pax6基因突变在某些先天性眼部疾病中可能的作用机制。方法采用Affymetrix基因芯片检测确定68个品系的BXD重组近交系(BXD RI)小鼠及其亲本C57BL/6J(B6)和DBA/2J(D2)小鼠、F1代眼组织中Pax6基因的差异表达。借助基因表达数量性状基因座(eQTL)分析方法,结合Gene Network网站的在线分析工具,研究Pax6基因表达上游调控基因,并进一步构建Pax6基因调控网络。结果 Pax6基因(1452526_a_at)在BXD RI小鼠的眼组织中呈高表达,不同品系小鼠表达量存在差异。Pax6基因具有1个显著性eQTL,位于19号染色体近测端,其似然比统计值达到15.80。磷酸肌醇4磷酸盐5激酶1α(Pip5k1a)是Pax6的上游调控候选基因。827个基因与Pax6基因具有高度遗传相关性(P<0.05)。结论 Pax6是一个反式调节基因;其表达量受上游调控候选基因Pip5k1a的调控。在Pax6基因突变导致先天性眼部疾病过程中涉及到细胞凋亡、脂质代谢、血管分化、细胞增殖和迁移等多种机制。更多还原

【Abstract】 Objective To investigate the possible mechanism of Pax6 gene mutations for inducing some congenital eye diseases.Methods Affymetrix microarray system was used to detect the differential expression of Pax6 gene in the eyes of C57BL/6J(B6),DBA/2J(D2)and BXD recombinant inbred(BXD RI)mice.The expression quantitative trait loci(eQTL)method and online analytical tool in Gene Network were approached to study the upstream regulatory gene of Pax6 and construct a genetic regulatory network of Pax6 gene.Results Pax6gene(1452526_a_at)was highly expressed in BXD RI mice and the expression was different among different strains of BXD RI mice.The genetic mapping for Pax6 gene showed that a significant eQTL located on proximal chromosome 19 with likelihood ratio statistic(LRS)score of 15.8.Pip5k1 awas identified as a candidate upstream gene of Pax6.Genetic regulatory network analysis showed that 827 genes were highly correlated with Pax6expression(P<0.05).Conclusion Pax6 is a transregulating gene,which is regulated by upstream candidate gene Pip5k1 a.Pax6gene mutation-induced congenital eye disease process involves a variety of mechanisms including apoptosis,lipid metabolism,vascular differentiation,cell proliferation and migration.更多还原