Genomic instability in Gadd45a-deficient mice
Genomic instability in Gadd45a-deficient mice
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DOI：
10.1038/13802
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发表时间：
1999-10-01
期刊：
影响因子：
30.8
通讯作者：
Fornace, AJ
中科院分区：
文献类型：
--
作者：
Hollander, MC;Sheikh, MS;Fornace, AJ
通过基因靶向产生的Gadd 45 a缺失小鼠表现出p53缺陷小鼠的几种表型特征，包括基因组不稳定性，增加的辐射致癌作用和低频率的露脑畸形。基因组不稳定的例子是非整倍体，染色体畸变，基因扩增和中心体扩增，并伴随着异常的有丝分裂，胞质分裂和生长控制。在Gadd 45 a（-/-）细胞系中，由于有丝分裂过程中出现多个纺锤体极，导致染色体的不均匀分离，这可能是造成非整倍体的原因之一。我们的研究结果表明，Gadd 45 a是p53通路的一个组成部分，有助于维持基因组的稳定性。
Gadd45a-null mice generated by gene targeting exhibited several of the phenotypes characteristic of p53-deficient mice, including genomic instability, increased radiation carcinogenesis and a low frequency of exencephaly. Genomic instability was exemplified by aneuploidy, chromosome aberrations, gene amplification and centrosome amplification, and was accompanied by abnormalities in mitosis, cytokinesis and growth control. Unequal segregation of chromosomes due to multiple spindle poles during mitosis occurred in several Gadd45a(-/-) cell lineages and may contribute to the aneuploidy. Our results indicate that Gadd45a is one component of the p53 pathway that contributes to the maintenance of genomic stability.