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.
出处
《军事医学》
CAS
CSCD
北大核心
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)