HIGH SUSCEPTIBILITY TO ULTRAVIOLET-INDUCED CARCINOGENESIS IN MICE LACKING XPC

COMPROMISE Of genetic information by mutation may result in the dysregulation of cellular growth control and subsequent tumour formation, Xeroderma pigmentosum (XP) is a rare autosomal disease characterized by hypersensitivity of the skin to sunlight and >1,000-fold increased risk of skin cancers in sun-exposed parts of the body, Cell fusion studies have revealed eight complementation groups In XP (A-G, and an XP-variant form); group C is one of the most common forms of the disease(1). We have isolated a mouse homologue of the human gene for XP group C and generated XPC-deficient mice by using embryonic stem cell technology. Mice homozygous for the XPC mutant allele (xpc(m1)/xpc(m1)) are viable and do not exhibit an increased susceptibility to spontaneous tumour generation at one year of age, However, xpc(m1)/xpc(m1) mice were found to be highly susceptible to ultraviolet-induced carcinogenesis compared with mice heterozygous for the mutant allele (xpc(m1)/+) and wild-type controls. Homozygous xpc(m1) mutant mice also display a spectrum of ultraviolet-exposure-related pathological skin and eye changes consistent with the human disease xeroderma pigmentosum group C.