| First Author | Wijnhoven SW | Year | 2007 |
| Journal | Mutat Res | Volume | 614 |
| Issue | 1-2 | Pages | 77-94 |
| PubMed ID | 16769089 | Mgi Jnum | J:118078 |
| Mgi Id | MGI:3698587 | Doi | 10.1016/j.mrfmmm.2005.12.018 |
| Citation | Wijnhoven SW, et al. (2007) Tissue specific mutagenic and carcinogenic responses in NER defective mouse models. Mutat Res 614(1-2):77-94 |
| abstractText | 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. |
