부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.mrfmmm.2005.12.018 Byline: Susan W.P. Wijnhoven (a), Esther M. Hoogervorst (a), Harm de Waard (b), Gijsbertus T.J. van der Horst (b), Harry van Steeg (a) Keywords: Nucleotide excision repair; Global genome repair; Transcription coupled repair; Mouse models; Xeroderma pigmentosum; Cockayne syndrome; Trichothiodystrophy; Segmental progeria; Inter-strand cross-link repair; Carcinogenesis; Mutagenesis; Chemical exposure Abstract: Several mouse models with defects in genes encoding components of the nucleotide excision repair (NER) pathway have been developed. In NER two different sub-pathways are known, i.e. transcription-coupled repair (TC-NER) and global-genome repair (GG-NER). A defect in one particular NER protein can lead to a (partial) defect in GG-NER, TC-NER or both. GG-NER defects in mice predispose to cancer, both spontaneous as well as UV-induced. As such these models (Xpa, Xpc and Xpe) recapitulate the human xeroderma pigmentosum (XP) syndrome. Defects in TC-NER in humans are associated with Cockayne syndrome (CS), a disease not linked to tumor development. Mice with TC-NER defects (Csa and Csb) are - except for the skin - not susceptible to develop (carcinogen-induced) tumors. Some NER factors, i.e. XPB, XPD, XPF, XPG and ERCC1 have functions outside NER, like transcription initiation and inter-strand crosslink repair. Deficiencies in these processes in mice lead to very severe phenotypes, like trichothiodystrophy (TTD) or a combination of XP and CS. In most cases these animals have a (very) short life span, display segmental progeria, but do not develop tumors. Here we will overview the available NER-related mouse models and will discuss their phenotypes in terms of (chemical-induced) tissue-specific tumor development, mutagenesis and premature aging features. Author Affiliation: (a) National Institute of Public Health and the Environment (RIVM), Laboratory of Toxicology, Pathology and Genetics, PO Box 1, 3720 BA, Bilthoven, The Netherlands (b) MGC, Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands Article History: Received 14 October 2005; Revised 23 December 2005; Accepted 28 December 2005