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

Jan De Boer, Jan De Wit, Harry Van Steeg, Rob J.W. Berg, Hans Morreau, Pim Visser, Alan R. Lehmann, Marinus Duran, Jan H.J. Hoeijmakers, Geert Weeda

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

179 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)981-990
Aantal pagina's10
TijdschriftMolecular Cell
Nummer van het tijdschrift7
StatusGepubliceerd - jun. 1998
Extern gepubliceerdJa


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