Age-related accumulation of autosomal mutations in solid tissues of the mouse is gender and cell type specific

Mitchell Turker, Michael Lasarev, Lanelle Connolly, Elizabeth Kasameyer, Deborah Roessler

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Most cancers in solid tissues increase with age and invariably contain causal mutations eliminating expression of one or more autosomal tumor suppressor genes. However, very little is known about the effect of age on autosomal mutations, often large in size, in cells of solid tissues. In this study, the frequency and spectrum of autosomal mutations were examined as a function of age for kidney epithelial cells and ear mesenchymal cells in B6D2F1 mice heterozygous for the selectable Aprt locus. Aprt mutant frequencies were found to increase with age in the kidneys of both male and female mice, but at all ages the mutant frequencies were approximately twice as high in the females, which in this strain have shorter lifespans than the males. An age-related increase in Aprt mutant frequencies was also observed for ear cells from female mice, but no significant increases in mutant frequencies were observed for the ear cells of male mice. A molecular analysis showed that the kidney and ear mutational spectra were distinct and that the age-related increases in mutant frequencies did not involve significant shifts in the mutational spectra. In total, the results demonstrate both gender and cell-type-specific patterns of autosomal mutational accumulation as a function of age in two solid tissues of the mouse.

Original languageEnglish (US)
Pages (from-to)73-86
Number of pages14
JournalAging Cell
Volume6
Issue number1
DOIs
Publication statusPublished - Feb 2007

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Keywords

  • Aging and cancer
  • Autosomal mutation
  • Mutant frequency
  • Mutational spectra
  • Somatic mutation

ASJC Scopus subject areas

  • Cell Biology

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