title: Age-related accumulation of autosomal mutations in solid tissues of the mouse is gender and cell type specific.
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.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology (CROET), Oregon Health and Science University, Portland, OR 97239, USA. turkerm@ohsu.edu
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Turker
authors.forename: Michael
authors.initials: M
authors.lastname: Lasarev
authors.forename: Lanelle
authors.initials: L
authors.lastname: Connolly
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kasameyer
authors.forename: Deborah
authors.initials: D
authors.lastname: Roessler
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000375:Aging / Q000235:genetics*; D000818:Animals; D004252:DNA Mutational Analysis; D004431:Ear, External / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D019656:Loss of Heterozygosity; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009154:Mutation / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D000228:Adenine Phosphoribosyltransferase