Nakane H, Takeuchi S, Yuba S, Saijo M, Nakatsu Y, Murai H, Nakatsuru Y, Ishikawa T, Hirota S, Kitamura Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Nature. 1995 Sep 14;377(6545):165-8. doi: 10.1038/377165a0.
Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.
着色性干皮病（XP）是一种常染色体隐性疾病，其特征为暴露于阳光下的部位皮肤癌高发以及出现神经并发症。XP在核苷酸切除修复（NER）的早期步骤存在缺陷，由八个不同的基因互补组（A - G组和一个变异组）组成。我们通过对小鼠胚胎干细胞（ES）进行基因靶向，建立了XPA（A组XP）基因缺陷小鼠。XPA缺陷小鼠既没有明显的身体异常，也没有病理改变，但在NER方面存在缺陷，并且对紫外线B或9,10 - 二甲基 - 1,2 - 苯并[a]蒽诱导的皮肤癌发生高度敏感。这些发现提供了体内证据，表明XPA蛋白可保护小鼠免受紫外线或化学致癌物引发的致癌作用。XPA缺陷小鼠可能为研究A组XP患者皮肤癌高发提供一个良好的体内模型。
