HIGH SUSCEPTIBILITY TO ULTRAVIOLET-INDUCED CARCINOGENESIS IN MICE LACKING XPC
HIGH SUSCEPTIBILITY TO ULTRAVIOLET-INDUCED CARCINOGENESIS IN MICE LACKING XPC
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DOI：
10.1038/377162a0
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发表时间：
1995-09-14
期刊：
影响因子：
64.8
通讯作者：
BRADLEY, A
中科院分区：
文献类型：
--
作者：
SANDS, AT;ABUIN, A;BRADLEY, A
突变对遗传信息的损害可能导致细胞生长控制的失调和随后的肿瘤形成，着色性干皮病（XP）是一种罕见的常染色体疾病，其特征是皮肤对阳光过敏，并且在身体暴露于阳光的部分中皮肤癌的风险增加> 1，000倍，细胞融合研究揭示了XP中的八个互补组。（A-G和XP变体形式）; C组是疾病最常见的形式之一（1）。我们已经分离出一个小鼠同源的人类基因XP组C和产生XPC缺陷小鼠，通过使用胚胎干细胞技术。XPC突变等位基因纯合子小鼠（xpc（m1）/xpc（m1））是可行的，并没有表现出增加的易感性自发肿瘤生成在一岁，但是，xpc（m1）/xpc（m1）小鼠被发现是高度敏感的紫外线诱导的致癌作用与小鼠杂合子突变等位基因（xpc（m1）/+）和野生型对照。纯合子xpc（m1）突变小鼠也显示出与人类着色性干皮病C组一致的紫外线暴露相关的皮肤和眼睛病理变化谱。
COMPROMISE Of genetic information by mutation may result in the dysregulation of cellular growth control and subsequent tumour formation, Xeroderma pigmentosum (XP) is a rare autosomal disease characterized by hypersensitivity of the skin to sunlight and >1,000-fold increased risk of skin cancers in sun-exposed parts of the body, Cell fusion studies have revealed eight complementation groups In XP (A-G, and an XP-variant form); group C is one of the most common forms of the disease(1). We have isolated a mouse homologue of the human gene for XP group C and generated XPC-deficient mice by using embryonic stem cell technology. Mice homozygous for the XPC mutant allele (xpc(m1)/xpc(m1)) are viable and do not exhibit an increased susceptibility to spontaneous tumour generation at one year of age, However, xpc(m1)/xpc(m1) mice were found to be highly susceptible to ultraviolet-induced carcinogenesis compared with mice heterozygous for the mutant allele (xpc(m1)/+) and wild-type controls. Homozygous xpc(m1) mutant mice also display a spectrum of ultraviolet-exposure-related pathological skin and eye changes consistent with the human disease xeroderma pigmentosum group C.