Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.
Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.
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发表时间：
1997-10
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通讯作者：
M. Mateyak;A. Obaya;Susumu Adachi;J. M. Sedivy
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作者：
M. Mateyak;A. Obaya;Susumu Adachi;J. M. Sedivy
构建了具有两个c-myc基因拷贝的靶向破坏的大鼠成纤维细胞系。虽然c-myc基因缺失细胞是可行的，但它们的生长明显受损。可检测的N-myc或L-myc表达的缺乏表明Myc功能对于细胞活力不是绝对必需的。c-myc无效表型是稳定的，并且可以通过引入c-myc转基因来逆转。指数生长的c-myc空细胞具有与其c-myc +/+亲本相同的细胞大小、rRNA和总蛋白含量，但RNA和蛋白质积累以及蛋白质降解的速率降低。细胞周期的G1期和G2期均显著延长，而S期的持续时间不受影响。这是第一次直接证明在G2中需要c-myc。G 0-->S转变是同步的，但S期进入明显延迟。本文报道的c-myc空细胞系是一个新的实验系统，用于研究假定的c-Myc靶基因的重要性，并确定参与细胞周期进展和凋亡的新的下游基因。
Rat fibroblast cell lines with targeted disruptions of both c-myc gene copies were constructed. Although c-myc null cells are viable, their growth is significantly impaired. The absence of detectable N-myc or L-myc expression indicates that Myc function is not absolutely essential for cell viability. The c-myc null phenotype is stable and can be reverted by introduction of a c-myc transgene. Exponentially growing c-myc null cells have the same cell size, rRNA, and total protein content as their c-myc +/+ parents, but the rates of RNA and protein accumulation as well as protein degradation are reduced. Both the G1 and G2 phases of the cell cycle are significantly lengthened, whereas the duration of S phase is unaffected. This is the first direct demonstration of a requirement for c-myc in G2. The G0-->S transition is synchronous, but S-phase entry is significantly delayed. The c-myc null cell lines reported here are a new experimental system in which to investigate the importance of putative c-Myc target genes and to identify novel downstream genes involved in cell cycle progression and apoptosis.