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A mouse model for the basal transcription/DNA repair syndrome trichothiodystrophy.

The sun-sensitive form of the severe neurodevelopmental, brittle hair disorder trichothiodystrophy (TTD) is caused by point mutations in the essential XPB and XPD helicase subunits of the dual functional DNA repair/basal transcription factor TFIIH. The phenotype is hypothesized to be in part derived from a nucleotide excision repair defect and in part from a subtle basal transcription deficiency accounting for the nonrepair TTD features. Using a novel gene-targeting strategy, we have mimicked the causative XPD point mutation of a TTD patient in the mouse. TTD mice reflect to a remarkable extent the human disorder, including brittle hair, developmental abnormalities, reduced life span, UV sensitivity, and skin abnormalities. The cutaneous symptoms are associated with reduced transcription of a skin-specific gene strongly supporting the concept of TTD as a human disease due to inborn defects in basal transcription and DNA repair.

Pubmed ID: 9651581

Authors

  • de Boer J
  • de Wit J
  • van Steeg H
  • Berg RJ
  • Morreau H
  • Visser P
  • Lehmann AR
  • Duran M
  • Hoeijmakers JH
  • Weeda G

Journal

Molecular cell

Publication Data

June 29, 1998

Associated Grants

None

Mesh Terms

  • Animals
  • Artificial Gene Fusion
  • Cells, Cultured
  • DNA Helicases
  • DNA Repair
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Female
  • Growth
  • Hair
  • Hair Diseases
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutagenesis, Site-Directed
  • Mutation
  • Proteins
  • Skin
  • Survival Analysis
  • Syndrome
  • Transcription Factors
  • Transcription, Genetic
  • Xeroderma Pigmentosum
  • Xeroderma Pigmentosum Group D Protein