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An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria.
Andressoo, Jaan-Olle Mitchell, James R Wit, Jan de Hoogstraten, Deborah Volker, Marcel Toussaint, Wendy Speksnijder, Ewoud Beems, Rudolf B Steeg, Harry van Jans, Judith
Andressoo, Jaan-Olle
Mitchell, James R
Wit, Jan de
Hoogstraten, Deborah
Volker, Marcel
Toussaint, Wendy
Speksnijder, Ewoud
Beems, Rudolf B
Steeg, Harry van
Jans, Judith
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Open Access
Type
Article
Language
en
Date of publication
2006-08-01
Year of publication
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An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria.
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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.