XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility

Daniel R. McNeill, Ping-Chang Lin, Marshall G. Miller, Paul J. Pistell, Nadja C. De Souza-Pinto, Kenneth W. Fishbein, Richard G. Spencer, Yie Liu, Christina Pettan-Brewer, Warren C. Ladiges, David M. Wilson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of ~26 months and a nearly identical maximal life expectancy of ~37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated-weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity-HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure.

Original languageEnglish (US)
Pages (from-to)7994-8002
Number of pages9
JournalNucleic Acids Research
Volume39
Issue number18
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Fingerprint

Haploinsufficiency
DNA Damage
Azoxymethane
Endoderm
Alkylating Agents
Disease Susceptibility
Telomere
Mesoderm
Life Expectancy
Inbred C57BL Mouse
Rupture
Mammals
Colon
Chromosomes
Biomarkers
Fats
Phenotype
Weights and Measures
Liver
Incidence

ASJC Scopus subject areas

  • Genetics

Cite this

McNeill, D. R., Lin, P-C., Miller, M. G., Pistell, P. J., De Souza-Pinto, N. C., Fishbein, K. W., ... Wilson, D. M. (2011). XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility. Nucleic Acids Research, 39(18), 7994-8002. https://doi.org/10.1093/nar/gkr280

XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility. / McNeill, Daniel R.; Lin, Ping-Chang; Miller, Marshall G.; Pistell, Paul J.; De Souza-Pinto, Nadja C.; Fishbein, Kenneth W.; Spencer, Richard G.; Liu, Yie; Pettan-Brewer, Christina; Ladiges, Warren C.; Wilson, David M.

In: Nucleic Acids Research, Vol. 39, No. 18, 01.10.2011, p. 7994-8002.

Research output: Contribution to journalArticle

McNeill, DR, Lin, P-C, Miller, MG, Pistell, PJ, De Souza-Pinto, NC, Fishbein, KW, Spencer, RG, Liu, Y, Pettan-Brewer, C, Ladiges, WC & Wilson, DM 2011, 'XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility', Nucleic Acids Research, vol. 39, no. 18, pp. 7994-8002. https://doi.org/10.1093/nar/gkr280
McNeill, Daniel R. ; Lin, Ping-Chang ; Miller, Marshall G. ; Pistell, Paul J. ; De Souza-Pinto, Nadja C. ; Fishbein, Kenneth W. ; Spencer, Richard G. ; Liu, Yie ; Pettan-Brewer, Christina ; Ladiges, Warren C. ; Wilson, David M. / XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility. In: Nucleic Acids Research. 2011 ; Vol. 39, No. 18. pp. 7994-8002.
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