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

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Abstract

XERODERM A 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 cancer1–3. Nucleo tide-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 damage4–7. 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−f− mice appear normal, at least until the age of 13 months. XPA−1− 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.

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Authors and Affiliations

  1. Department of Immunology, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Annemieke de Vries, Frans M. A. Hofhuis, Peter J. A. Capel & Sjef J. Verbeek

  2. Department of Dermatology, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Rob J. W. Berg & Frank R. de Gruijl

  3. Laboratories of Carcinogenesis and Mutagenesis, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA, Bilthoven, The Netherlands

    Annemieke de Vries, Conny Th. M. van Oostrom, Coen F. van Kreijl & Harry van Steeg

  4. Laboratory of Pathology, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA, Bilthoven, The Netherlands

    Paul M. Dortant & Piet W. Wester

Authors
  1. Annemieke de Vries
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  2. Conny Th. M. van Oostrom
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  3. Frans M. A. Hofhuis
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  4. Paul M. Dortant
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  5. Rob J. W. Berg
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  6. Frank R. de Gruijl
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  7. Piet W. Wester
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  8. Coen F. van Kreijl
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  9. Peter J. A. Capel
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  10. Harry van Steeg
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  11. Sjef J. Verbeek
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Vries, A., van Oostrom, C., Hofhuis, F. et al. Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA. Nature 377, 169–173 (1995). https://doi.org/10.1038/377169a0

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