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  • Title: Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma pigmentosum group A (XPA) model mice.
    Author: Miyauchi-Hashimoto H, Tanaka K, Horio T.
    Journal: J Invest Dermatol; 1996 Sep; 107(3):343-8. PubMed ID: 8751968.
    Abstract:
    Xeroderma pigmentosum group A (XPA) gene-deficient mice were developed by gene targeting in mouse embryonic stem cells. To examine whether these XPA-model mice display photodermatologic abnormalities similar to those in human xeroderma pigmentosum, we investigated the effects of acute ultraviolet radiation on the homozygous (-/-) mice compared to the wild type (+/+) and heterozygous (+/-) mice. A single irradiation with ultraviolet B or topical psoralen plus ultraviolet A treatment induced stronger and longer lasting ear swelling in the (-/-) mice than in the (+/+) and (+/-) mice. Histologic changes including epidermal necrosis, cell infiltration, and sunburn cell formation after ultraviolet B radiation were more prominent in the (-/-) model mice than in the control mice. The (-/-) model mice showed damage of ADPase(+)Langerhans cells at a lower ultraviolet B dose than did the control mice. Moreover, the reappearance of ADPase(+)Langerhans cells after ultraviolet B radiation was delayed in the (-/-) mice compared to the control mice. Although contact hypersensitivity was induced equally in all mice, ultraviolet B-induced local and systemic immunosuppression were greatly enhanced in the (-/-) model mice. The data suggest that the XPA gene-deficient mice may be a useful model of human XPA, because the responses to UV radiation in the mice were very similar to those in the patients with XPA. Moreover, it is possible that enhanced ultraviolet immunosuppression is involved in the development of skin cancers in xeroderma pigmentosum.
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