Bois P, Collick A, Brown J, Jeffreys A J
Department of Genetics, University of Leicester, UK.
Hum Mol Genet. 1997 Sep;6(9):1565-71. doi: 10.1093/hmg/6.9.1565.
Human minisatellite MS32 (D1S8) shows instability both in the germline and, at much lower levels, in somatic DNA. To investigate factors that influence somatic and germline mutation, large cosmid-based constructs containing MS32 were introduced into mice, bred to homozygosity and tested for instability in blood and sperm. Analysis of single copy and multicopy transgenic lines revealed somatic mutants occurring at a frequency comparable with that seen in man. As in humans, these mutants arose mainly by simple intra-allelic duplications and deletions. In contrast, analysis of sperm DNA from four different transgenic lines showed no trace of the complex recombination-based germline instability seen in man, even using PCR-based approaches capable of detecting very rare mutants. These data provide further evidence that germline and somatic mutation at human minisatellite MS32 occur via distinct pathways, that a major barrier exists to the transfer of germline instability from humans to mice and that the mouse germline appears to be protected from mitotic instability of the type seen in blood.
人类小卫星MS32（D1S8）在种系中以及在低得多的水平上在体细胞DNA中均表现出不稳定性。为了研究影响体细胞和种系突变的因素，将含有MS32的基于黏粒的大型构建体导入小鼠，培育至纯合状态，并检测血液和精子中的不稳定性。对单拷贝和多拷贝转基因系的分析显示，体细胞突变体出现的频率与人中所见频率相当。与人类一样，这些突变体主要通过简单的等位基因内重复和缺失产生。相比之下，对来自四个不同转基因系的精子DNA的分析显示，即使使用能够检测非常罕见突变体的基于PCR的方法，也未发现人类中所见的基于复杂重组的种系不稳定性的痕迹。这些数据进一步证明，人类小卫星MS32的种系和体细胞突变通过不同途径发生，存在一个将种系不稳定性从人类转移到小鼠的主要障碍，并且小鼠种系似乎受到保护，免受血液中所见类型的有丝分裂不稳定性的影响。
