title: High susceptibility to ultraviolet-induced carcinogenesis in mice lacking XPC.
abstract: 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. 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 (xpcm1/xpcm1) are viable and do not exhibit an increased susceptibility to spontaneous tumour generation at one year of age. However, xpcm1/xpcm1 mice were found to be highly susceptible to ultraviolet-induced carcinogenesis compared with mice heterozygous for the mutant allele (xpcm1/+) and wild-type controls. Homozygous xpcm1 mutant mice also display a spectrum of ultraviolet-exposure-related pathological skin and eye changes consistent with the human disease xeroderma pigmentosum group C.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Sands
authors.forename: A
authors.initials: A
authors.lastname: Abuin
authors.forename: A
authors.initials: A
authors.lastname: Sanchez
authors.forename: C J
authors.initials: CJ
authors.lastname: Conti
authors.forename: A
authors.initials: A
authors.lastname: Bradley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004249:DNA Damage; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000528:radiation effects; D017353:Gene Deletion; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C501002:Xpc protein, mouse; C086984:XPC protein, human