A Mouse Model for the Basal Transcription/DNA Repair Syndrome Trichothiodystrophy
| Autor: | Hans Morreau, Harry van Steeg, Marinus Duran, Alan R. Lehmann, R. J. W. Berg, Geert Weeda, Pim Visser, Jan de Wit, Jan de Boer, Jane H.J. Hoeijmakers |
|---|---|
| Přispěvatelé: | Molecular Genetics |
| Rok vydání: | 1998 |
| Předmět: |
Male
DNA Repair Transcription Genetic DNA repair Trichothiodystrophy Growth Mice Transcription (biology) medicine Animals Humans Molecular Biology Cells Cultured Skin Xeroderma Pigmentosum Group D Protein Xeroderma Pigmentosum integumentary system biology General transcription factor Point mutation DNA Helicases Proteins Helicase Syndrome Cell Biology medicine.disease Survival Analysis Molecular biology Mice Mutant Strains Artificial Gene Fusion DNA-Binding Proteins Mice Inbred C57BL Disease Models Animal Mutation Mutagenesis Site-Directed biology.protein Transcription factor II H Cancer research Female Hair Diseases Hair Transcription Factors Nucleotide excision repair |
| Zdroj: | Molecular Cell, 1, 981-990. Cell Press |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(00)80098-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|