A. Devries et al., INCREASED SUSCEPTIBILITY TO ULTRAVIOLET-B AND CARCINOGENS OF MICE LACKING THE DNA EXCISION-REPAIR GENE XPA, Nature, 377(6545), 1995, pp. 169-173
XERODERMA pigmentosum patients with a defect in the nucleotide-excisio
n repair gene XPA are characterized by, for example, a >1,000-fold hig
her risk of developing sunlight-induced skin cancer(1-3). Nucleotide-e
xcision repair (NER) is involved in the removal of a wide spectrum of
DNA lesions, The XPA protein functions in a pre-incision step, the rec
ognition of DNA damage(4-7). To permit tile functional analysis of the
XPA gene in vivo, we have generated XPA-deficient mice by gene target
ing in embryonic stem cells, The YPA(-/-) mice appear normal, at least
until the age of 13 months, XPA(-/-) mice are highly susceptible to u
ltraviolet (UV)-B-induced skin and eye tumours and to 7,12-dimethylben
z[a]anthracene (DMBA)-induced skin tumours, We conclude that the XPA-d
eficient mice strongly mimic the phenotype of humans with xeroderma pi
gmentosum.