title: A mouse model for the basal transcription/DNA repair syndrome trichothiodystrophy.
abstract: 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.
authors.affiliation: MGC-Department of Cell Biology and Genetics Erasmus University, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: de Boer
authors.forename: J
authors.initials: J
authors.lastname: de Wit
authors.forename: H
authors.initials: H
authors.lastname: van Steeg
authors.forename: R J
authors.initials: RJ
authors.lastname: Berg
authors.forename: H
authors.initials: H
authors.lastname: Morreau
authors.forename: P
authors.initials: P
authors.lastname: Visser
authors.forename: A R
authors.initials: AR
authors.lastname: Lehmann
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: J H
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: G
authors.initials: G
authors.lastname: Weeda
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D002478:Cells, Cultured; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005260:Female; D006128:Growth / Q000235:genetics / Q000502:physiology; D006197:Hair / Q000002:abnormalities; D006201:Hair Diseases / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; C497293:Ercc2 protein, mouse