Buettner V L, Hill K A, Scaringe W A, Sommer S S
Department of Molecular Genetics, City of Hope/Beckman Research Institute, 91010, Duarte, CA 91010, USA.
Mutat Res. 2000 Sep 18;452(2):219-29. doi: 10.1016/s0027-5107(00)00090-7.
To characterize the nature of multiple mutations in the tissues of an intact animal, the Big Blue transgenic mouse mutation detection system was used to examine 1459 mutants from eight normal tissues and 507 mutants from 11 tumors. Multiple mutations occurred and predominantly doublet mutants were identified (i.e. two mutations within one mutant lacI gene), but multiplets of up to five mutations were observed. The frequency of doublets in normal tissues and spontaneous tumors from p53-deficient mice was enhanced to the same degree (660 and 667 fold, respectively) over that expected for two independent mutational events. Doublets, multiplets and singlets have similar patterns of mutation. The distance between mutations in doublets fits an exponential distribution, not that expected for randomly spaced events, suggesting that many doublets occur in rapid succession within the same cell cycle.
为了表征完整动物组织中多个突变的性质，使用大蓝转基因小鼠突变检测系统检查了来自八个正常组织的1459个突变体和来自11个肿瘤的507个突变体。发生了多个突变，并且主要鉴定出双突变体（即一个突变的lacI基因内有两个突变），但观察到多达五个突变的多重突变体。与两个独立突变事件预期的频率相比，p53缺陷小鼠的正常组织和自发肿瘤中的双突变体频率提高到相同程度（分别为660倍和667倍）。双突变体、多重突变体和单突变体具有相似的突变模式。双突变体中突变之间的距离符合指数分布，而不是随机间隔事件预期的分布，这表明许多双突变体在同一细胞周期内迅速连续发生。
