HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Cited by other online articles Google Scholar Articles by Jackson, A. U. Articles by Miller, R. A. Articles citing this Article PubMed PubMed Citation Articles by Jackson, A. U. Articles by Miller, R. A.

Mouse Loci Associated With Life Span Exhibit Sex-Specific and Epistatic Effects

^a Department of Human Genetics, University of Michigan School of Medicine,
^b Institute of Gerontology, University of Michigan, Ann Arbor
^c Ann Arbor VA Medical Center, University of Michigan, Ann Arbor
^d Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor

Richard A. Miller, The Geriatrics Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940 E-mail: millerr{at}umich.edu.

Decision Editor: Edward Masoro, PhD

We have looked for genetic predictors of life span in a sibship of mice created as a four-way cross among inbred grandparental strains BALB/cJ, C57BL/6J, C3H/HeJ, and DBA/2J. To minimize the potential confounding effects of loci that influence early-life illnesses only, we conducted two analyses: one involving all the mice, and the other using a data set from which the first 20% of the deaths were excluded. The two strongest associations reach experimentwise significance levels (p < .01) when tested on the 80% of the mice with the longest life spans. Surprisingly, three of the four strongest associations showed sex-specific effects, with an influence on life span of either male or female mice, but not both. Epistatic interactions among the loci were also identified. The life-span effect of a locus on chromosome 10 (D10Mit15) exhibited epistatic interactions with loci on chromosomes 9 and 16 (D9Mit10 and D16Mit182). In a second example, a locus on chromosome 12 (D12Mit167) depended on the specific combination of alleles inherited from both male and female parents. Our results show that the common laboratory mouse strains are polymorphic at loci that produce substantial differences in life span and that these effects can be sex specific and conditional on alleles inherited at other loci.

This article has been cited by other articles: (Search Google Scholar for Other Citing Articles)

				A. Kriete Biomarkers of Aging: Combinatorial or Systems Model? Sci. Aging Knowl. Environ., January 4, 2006; 2006(1): pe1 - pe1. [Abstract] [Full Text]

				J. K. Quarrie and K. T. Riabowol Murine Models of Life Span Extension Sci. Aging Knowl. Environ., August 4, 2004; 2004(31): re5 - re5. [Abstract] [Full Text] [PDF]

				N. Wolf, A. Galecki, R. Lipman, S. Chen, M. Smith-Wheelock, D. Burke, and R. Miller Quantitative Trait Locus Mapping for Age-Related Cataract Severity and Synechia Prevalence Using Four-Way Cross Mice Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1922 - 1929. [Abstract] [Full Text] [PDF]

				R. N. Butler, S. N. Austad, N. Barzilai, A. Braun, S. Helfand, P. L. Larsen, A. M. McCormick, T. T. Perls, A. R. Shuldiner, R. L. Sprott, and H. R. Warner Longevity Genes: From Primitive Organisms to Humans J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): B581 - 584. [Full Text] [PDF]

				J. W. Curtsinger Sex Specificity, Life-Span QTLs, and Statistical Power J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2002; 57(12): B409 - 414. [Abstract] [Full Text] [PDF]

				R. A. Miller, C. Chrisp, A. U. Jackson, A. T. Galecki, and D. T. Burke Coordinated Genetic Control of Neoplastic and Nonneoplastic Diseases in Mice J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2002; 57(1): B3 - 8. [Abstract] [Full Text] [PDF]