Abstract
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)1. 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-l,2-benz[a]anthra-cene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XP A -deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.
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Nakane, H., Takeuchi, S., Yuba, S. et al. High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene. Nature 377, 165–168 (1995). https://doi.org/10.1038/377165a0
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DOI: https://doi.org/10.1038/377165a0
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