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 RIS Download
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