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

XERODERMA 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 cancer. Nucleotide-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 damage. 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-1- 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. (Author)