High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene.
Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.
Nakane
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Takeuchi
S
S
Yuba
S
S
Saijo
M
M
Nakatsu
Y
Y
Murai
H
H
Nakatsuru
Y
Y
Ishikawa
T
T
Hirota
S
S
Kitamura
Y
Y
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D015127:9,10-Dimethyl-1,2-benzanthracene