缺乏DNA切除修复基因XPA的小鼠对紫外线B和致癌物的易感性增加。

Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA.

作者信息

de Vries A, van Oostrom C T, Hofhuis F M, Dortant P M, Berg R J, de Gruijl F R, Wester P W, van Kreijl C F, Capel P J, van Steeg H, Verbeek S J

机构信息

Department of Immunology, University of Utrecht, The Netherlands.

出版信息

Nature. 1995 Sep 14;377(6545):169-73. doi: 10.1038/377169a0.

DOI:10.1038/377169a0

PMID:7675086

Abstract

Xeroderma pigmentosum patients with a defect in the nucleotide-excision repair gene XPA are characterized by, for example, a > 1,000-fold higher risk of developing sunlight-induced skin cancer. Nucleotide-excision repair (NER) is involved in the removal of a wide spectrum of DNA lesions. The XPA protein functions in a pre-incision step, the recognition of DNA damage. To permit the functional analysis of the XPA gene in vivo, we have generated XPA-deficient mice by gene targeting in embryonic stem cells. The XPA-/-mice appear normal, at least until the age of 13 months. XPA-/-mice are highly susceptible to ultraviolet (UV)-B-induced skin and eye tumours and to 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumours. We conclude that the XPA-deficient mice strongly mimic the phenotype of humans with xeroderma pigmentosum.

摘要

患有核苷酸切除修复基因XPA缺陷的着色性干皮病患者的特征是，例如，患阳光诱导皮肤癌的风险高出1000倍以上。核苷酸切除修复（NER）参与多种DNA损伤的清除。XPA蛋白在切口前步骤即DNA损伤识别中发挥作用。为了在体内对XPA基因进行功能分析，我们通过在胚胎干细胞中进行基因靶向产生了XPA缺陷小鼠。XPA-/-小鼠看起来正常，至少在13个月龄之前如此。XPA-/-小鼠对紫外线（UV）-B诱导的皮肤和眼部肿瘤以及7,12-二甲基苯并[a]蒽（DMBA）诱导的皮肤肿瘤高度敏感。我们得出结论，XPA缺陷小鼠强烈模拟了着色性干皮病患者的表型。