Shao Changshun, Yin Moying, Deng Li, Stambrook Peter J, Doetschman Thomas, Tischfield Jay A
Department of Genetics, Rutgers, the State University of New Jersey, Piscataway, New Jersey, NJ 08854-8082, USA.
Oncogene. 2002 Apr 25;21(18):2840-5. doi: 10.1038/sj.onc.1205358.
Mice null for the Pms2 mismatch repair (MMR) gene exhibit a predisposition to lymphoma, microsatellite repeat instability, and failure of spermatogenesis. To study the role of Pms2 in the maintenance of in vivo genomic integrity in somatic cells, we characterized Aprt mutations in T cells and fibroblasts of 129 x C3H Pms2-/-Aprt+/- mice. The spontaneous frequency of DAP-resistant T lymphocytes, as a consequence of APRT-deficiency, was increased threefold. Point mutation, which accounted for less than 20% of the DAP(r) mutant clones in Pms2+/+ mice, was predominant in the mutant T cell clones from Pms2-/- mice. These point mutations were predominantly TA to CG transitions. Fibroblasts of Pms2-/- mice exhibited only a modest increase in the frequency of clones with point mutations, such that mitotic recombination was still the primary cause of APRT deficiency. Thus, the mutator phenotype as a consequence of PMS2 deficiency is tissue-dependent, which may be related to the tissue-specific tumor proneness of Pms2-/- mice.
Pms2错配修复（MMR）基因缺失的小鼠易患淋巴瘤、微卫星重复序列不稳定以及精子发生障碍。为了研究Pms2在维持体细胞体内基因组完整性中的作用，我们对129 x C3H Pms2-/-Aprt+/-小鼠的T细胞和成纤维细胞中的Aprt突变进行了特征分析。由于APRT缺乏，抗DAP T淋巴细胞的自发频率增加了三倍。在Pms2+/+小鼠中，点突变占DAP(r)突变克隆的比例不到20%，而在Pms2-/-小鼠的突变T细胞克隆中占主导地位。这些点突变主要是TA到CG的转换。Pms2-/-小鼠的成纤维细胞中，点突变克隆的频率仅适度增加，因此有丝分裂重组仍是APRT缺乏的主要原因。因此，PMS2缺乏导致的突变表型具有组织依赖性，这可能与Pms2-/-小鼠的组织特异性肿瘤易感性有关。
