High Incidence of ultraviolet-B-or Chemical-Carcinogen-Induced Skin Tumours in Mice Lacking the Xeroderma Pigmentosum Group A Gene

Nature. 1995 Sep 14;377(6545):165-8. doi: 10.1038/377165a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Cell Line
  • Cloning, Molecular
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Female
  • Gene Deletion
  • Gene Targeting
  • Incidence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Neoplasms, Radiation-Induced / epidemiology
  • Neoplasms, Radiation-Induced / genetics*
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics*
  • Ultraviolet Rays*
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum Group A Protein

Substances

  • DNA-Binding Proteins
  • Xeroderma Pigmentosum Group A Protein
  • Xpa protein, mouse
  • 9,10-Dimethyl-1,2-benzanthracene