de Boer J G, Erfle H, Walsh D, Holcroft J, Provost J S, Rogers B, Tindall K R, Glickman B W
Department of Biology, University of Victoria, British Columbia, Canada.
Environ Mol Mutagen. 1997;30(3):273-86.
The advent of transgenic technology has greatly facilitated the study of mutation in animals in vivo. The Big Blue mouse system, transgenic for the lacI gene, permits not only the quantification of mutations in different tissues but also provides for the generation of in vivo-derived mutational spectra. This report details the sequence alterations of 348 spontaneous mutations recovered from the liver of 6-8-week-old male Big Blue mice. The spectra recovered from two strains of mice, C57BI/6 and B6C3F1, were compared and found to be very similar. The predominant mutations are G:C-->A:T transitions, with 75% of these occurring at 5'-CpG-3' sequences. This mutational bias is consistent with deamination-directed mutation at methylated cytosine bases. The second most common class of mutations is G:C-->T:A transversions. A significant clonal expansion of mutants was found in several animals, and this was used to make an approximate correction of the mutant frequency such that the most conservative estimate of mutation frequency is presented. The establishment of this substantial database of spontaneous mutations in the liver of Big Blue mice is intended to serve as a reference against which mutations recovered after treatment can be compared.
转基因技术的出现极大地促进了对动物体内突变的研究。携带lacI基因的转基因“大蓝”鼠系统不仅能对不同组织中的突变进行定量，还能生成体内衍生的突变谱。本报告详细介绍了从6 - 8周龄雄性“大蓝”鼠肝脏中回收的348个自发突变的序列改变。比较了从C57BI/6和B6C3F1两个品系小鼠中获得的突变谱，发现它们非常相似。主要的突变是G:C→A:T转换，其中75%发生在5'-CpG-3'序列。这种突变偏向与甲基化胞嘧啶碱基的脱氨基导向突变一致。第二常见的突变类型是G:C→T:A颠换。在几只动物中发现了突变体的显著克隆扩增，并以此对突变频率进行了近似校正，从而给出了最保守的突变频率估计。建立这个关于“大蓝”鼠肝脏自发突变的庞大数据库，旨在作为一个参考，用于比较处理后回收的突变。
