RBBP6敲除小鼠胚胎致死原因的探讨  

Analysis of the causes of RBBP6^(-/-) embryonic lethality

作　　者：徐亮[1,2] 李大虎[2] 谢萍[2] 王少霞[2] 李杨[2] 彭瑞云[2] 张令强[1,2] 汪思应[1] 

机构地区：[1]安徽医科大学病理学与病理生理学系,合肥230032 [2]军事医学科学院放射与辐射医学研究所,北京蛋白质组研究中心,蛋白质组学国家重点实验室,北京100850

出　　处：《军事医学》2012年第7期524-527,530,共5页Military Medical Sciences

基　　金：国家自然科学基金资助项目(31125010);国家973计划资助项目(2011CB910802)

摘　　要：目的探索成视网膜细胞瘤基因结合蛋白6(Rb binding protein 6,RBBP6)基因敲除小鼠胚胎致死的原因。方法敲低细胞内源性RBBP6后检测磷酸化组蛋白H2AX(phosphorylated histone H2AX,γH2AX)的蛋白水平,利用免疫组化检测RBBP6-/-小鼠胚胎中γH2AX的蛋白水平,由此分析两者的相关性。结果 RBBP6敲低的细胞中γH2AX蛋白水平显著上调,RBBP6-/-小鼠胚胎中γH2AX的蛋白水平也明显上调。结论 RBBP6-/-小鼠胚胎中γH2AX蛋白水平显著升高,从而引发基因组的不稳定性,是RBBP6-/-小鼠胚胎致死的原因之一,并提示RBBP6可能参与DNA损伤应答。Objective To analyze the causes of RBBP6 -/- embryonic lethality. Methods To investigate whether genetic interaction between RBBP6 and 3,H2AX plays a role in embryonic survival, endogenous RBBP6 was knocked down by RNA interference （RNAi）, and the protein level of TH2AX was examined by Western blot. Immunohistochemistry was used to examine the expression of γH2AX in RBBP6-/- mouse embryos. Results It was discovered that γ/H2AX protein level increased after the knockdown of RBBP6. Meanwhile γ/H2AX level was also notably up-regulated in RBBP6 -/- mousc embryos compared to their wild-type littermates. Conclusion 3,H2AX is greatly increased after the knockdown of RBBP6, suggesting that the decline of RBBP6 result in genome instability. These data also help explain the causes of RBBP6-/- embryonic lethality.

关 键 词：RBBP6 DNA损伤 γH2AX 免疫组化 小鼠 基因敲除 

分 类 号：R346[医药卫生—基础医学]