An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria

Andressoo, Jaan-Olle, Mitchell, James R, de Wit, Jan, Hoogstraten, Deborah, Volker, Marcel, Toussaint, Wendy, Speksnijder, Ewoud, Beems, Rudolph B, van Steeg, Harry, Jans, Judith, de Zeeuw, Chris I, Jaspers, Nicolaas G J, Raams, Anja, Lehmann, Alan R, Vermeulen, Wim, Hoeijmakers, Jan H J and van der Horst, Gijsbertus T J (2006) An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria. Cancer Cell, 10 (2). pp. 121-132. ISSN 1535-6108

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Abstract

Inborn defects in nucleotide excision DNA repair (NER) can paradoxically result in elevated cancer incidence (xeroderma pigmentosum [XP]) or segmental progeria without cancer predisposition (Cockayne syndrome [CS] and trichothiodystrophy [TTD]). We report generation of a knockin mouse model for the combined disorder XPCS with a G602D-encoding mutation in the Xpd helicase gene. XPCS mice are the most skin cancer-prone NER model to date, and we postulate an unusual NER dysfunction that is likely responsible for this susceptibility. XPCS mice also displayed symptoms of segmental progeria, including cachexia and progressive loss of germinal epithelium. Like CS fibroblasts, XPCS and TTD fibroblasts from human and mouse showed evidence of defective repair of oxidative DNA lesions that may underlie these segmental progeroid symptoms.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Marcel Volker
Date Deposited: 06 Feb 2012 21:20
Last Modified: 26 Jul 2016 14:44
URI: http://sro.sussex.ac.uk/id/eprint/30814
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