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

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 R. Lehmann; Wim Vermeulen; Jan H.J. Hoeijmakers; Gijsbertus T.J. van der Horst

doi:10.1016/j.ccr.2006.05.027

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

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 R. Lehmann, Wim Vermeulen, Jan H.J. Hoeijmakers, Gijsbertus T.J. van der Horst

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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.

Original language	English
Pages (from-to)	121-132
Number of pages	12
Journal	Cancer Cell
Volume	10
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2006.05.027
Publication status	Published - Aug 2006
Externally published	Yes

Keywords

DNA

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Andressoo, J. O., Mitchell, J. R., de Wit, J., Hoogstraten, D., Volker, M., Toussaint, W., Speksnijder, E., Beems, R. B., van Steeg, H., Jans, J., de Zeeuw, C. I., Jaspers, N. G. J., Raams, A., Lehmann, A. R., Vermeulen, W., Hoeijmakers, J. H. J., & van der Horst, G. 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), 121-132. https://doi.org/10.1016/j.ccr.2006.05.027

@article{cd4ee510d03a40efac75abbff5478627,

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

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.",

keywords = "DNA",

author = "Andressoo, {Jaan Olle} and Mitchell, {James R.} and {de Wit}, Jan and Deborah Hoogstraten and Marcel Volker and Wendy Toussaint and Ewoud Speksnijder and Beems, {Rudolph B.} and {van Steeg}, Harry and Judith Jans and {de Zeeuw}, {Chris I.} and Jaspers, {Nicolaas G.J.} and Anja Raams and Lehmann, {Alan R.} and Wim Vermeulen and Hoeijmakers, {Jan H.J.} and {van der Horst}, {Gijsbertus T.J.}",

note = "Funding Information: This research was supported by the Netherlands Organization for Scientific Research (NWO) through the foundation of the Research Institute for Diseases in the Elderly, as well as grants from the NIH (1PO1 AG17242-02), NIEHS (1UO1 ES011044), EC (QRTL-1999-02002), Dutch Cancer Society (EUR 99-2004), and AICR (05-280). J.R.M. was a fellow of the Damon Runyon Cancer Research Fund (DRG 1677). We are grateful to Ruud Koppenol for photography; Brent Calder, Paul Lohman, and Yurii Aulchenko for statistical analyses; and Diederik van Deursen for plasmid reagents. J.H.J.H. is founder of DNage, a company in the field of aging and aging-related diseases. ",

year = "2006",

month = aug,

doi = "10.1016/j.ccr.2006.05.027",

language = "English",

volume = "10",

pages = "121--132",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "2",

}

Andressoo, JO, Mitchell, JR, de Wit, J, Hoogstraten, D, Volker, M, Toussaint, W, Speksnijder, E, Beems, RB, van Steeg, H, Jans, J, de Zeeuw, CI, Jaspers, NGJ, Raams, A, Lehmann, AR, Vermeulen, W, Hoeijmakers, JHJ & van der Horst, GTJ 2006, 'An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria', Cancer Cell, vol. 10, no. 2, pp. 121-132. https://doi.org/10.1016/j.ccr.2006.05.027

TY - JOUR

T1 - An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria

AU - Andressoo, Jaan Olle

AU - Mitchell, James R.

AU - de Wit, Jan

AU - Hoogstraten, Deborah

AU - Volker, Marcel

AU - Toussaint, Wendy

AU - Speksnijder, Ewoud

AU - Beems, Rudolph B.

AU - van Steeg, Harry

AU - Jans, Judith

AU - de Zeeuw, Chris I.

AU - Jaspers, Nicolaas G.J.

AU - Raams, Anja

AU - Lehmann, Alan R.

AU - Vermeulen, Wim

AU - Hoeijmakers, Jan H.J.

AU - van der Horst, Gijsbertus T.J.

N1 - Funding Information: This research was supported by the Netherlands Organization for Scientific Research (NWO) through the foundation of the Research Institute for Diseases in the Elderly, as well as grants from the NIH (1PO1 AG17242-02), NIEHS (1UO1 ES011044), EC (QRTL-1999-02002), Dutch Cancer Society (EUR 99-2004), and AICR (05-280). J.R.M. was a fellow of the Damon Runyon Cancer Research Fund (DRG 1677). We are grateful to Ruud Koppenol for photography; Brent Calder, Paul Lohman, and Yurii Aulchenko for statistical analyses; and Diederik van Deursen for plasmid reagents. J.H.J.H. is founder of DNage, a company in the field of aging and aging-related diseases.

PY - 2006/8

Y1 - 2006/8

N2 - 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.

AB - 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.

KW - DNA

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U2 - 10.1016/j.ccr.2006.05.027

DO - 10.1016/j.ccr.2006.05.027

M3 - Article

C2 - 16904611

AN - SCOPUS:33746973285

SN - 1535-6108

VL - 10

SP - 121

EP - 132

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

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

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Keywords

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