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

journal contribution
posted on 2023-06-08, 09:42 authored by Jaan-Olle Andressoo, James R Mitchell, Jan de Wit, Deborah Hoogstraten, Marcel Volker, Wendy Toussaint, Ewoud Speksnijder, Rudolph B Beems, Harry van Steeg, Judith Jans, Chris I de Zeeuw, Nicolaas G J Jaspers, Anja Raams, Alan LehmannAlan Lehmann, Wim Vermeulen, Jan H J Hoeijmakers, Gijsbertus T J van der Horst
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.

History

Publication status

  • Published

Journal

Cancer Cell

ISSN

1535-6108

Publisher

Elsevier

Issue

2

Volume

10

Page range

121-132

Pages

12.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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