High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene

• DOI: 10.1038/377165a0
• Publication Date: 2003-06-12T23:55:46Z
• Authors: Hironobu Nakane; Seiji Takeuchi; Shunsuke Yuba; Masafumi Saijo; Yoshimichi Nakatsu; Hiroaki Murai; Yoko Nakatsuru; Takatoshi Ishikawa; Seiichi Hirota; Yukihiko Kitamura; Yoko Kato; Yukio Tsunoda; Hiroko Miyauchi; Takeshi Horio; Tomoyuki Tokunaga; Tsukasa Matsunaga; Osamu Nikaido; Yoshitake Nishimune; Yoshio Okada; Kiyoji Tanaka
• Keywords: Male; 0301 basic medicine; Xeroderma Pigmentosum; Neoplasms, Radiation-Induced; Skin Neoplasms; DNA Repair; Ultraviolet Rays; 9,10-Dimethyl-1,2-benzanthracene; Incidence; Cell Line; Xeroderma Pigmentosum Group A Protein; 3. Good health; DNA-Binding Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Gene Targeting; Mice, Inbred CBA; Animals; Female; Cloning, Molecular; Gene Deletion

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.