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AGE

, 37:9 | Cite as

Genetic analysis of a murine QTL for diet restriction on chromosome 15

  • Breanne L. NewellEmail author
  • Katerina Kechris
  • Matt B. McQueen
  • Thomas E. Johnson
Article

Abstract

Diet restriction (DR), the implementation of a reduced calorie diet, without starvation, increases lifespan in a number of model organisms including mammals. How DR extends lifespan remains unclear. Genetic studies have shown that life extension is not a universal response to DR; instead, the effects of DR are strain dependent. We previously mapped a quantitative trait locus (QTL) specifying differential response to DR to chromosome 15 in the inbred long-sleep (ILS) × inbred short-sleep (ISS) recombinant inbred panel of mice. This QTL named Fedr2 (fuel efficiency response to DR)-2 modifies body weight (BW) and hair growth (HG) in response to DR. The QTL has been previously mapped using the ISS.Lore5LA (5LA) congenic strain. Here, we have used the reciprocal congenic strain ILS.Lore5SA (5SA) to further investigate Fedr2. The 5LA congenic showed increased ability to maintain BW and HG under DR. For the reciprocal congenic, 5SA, we expected the reciprocal response that the 5SA congenic would have a lesser ability to maintain BW and HG under DR. This expectation was mostly met. The Fedr2 S allele conferred lower BW maintenance under DR in both females and males. For females, the difference in BW was significant for the entirety of DR, and for males, the difference became significant at week 17 of DR. For HG, the Fedr2 S allele conferred decreased HG ability under DR in males, but not for females. These results highlight the genetic basis for variation in DR response and support the previous observations that Fedr2 mediates BW and HG during DR.

Keywords

Diet restriction Murine Congenic Body weight Hair growth QTL 

Notes

Acknowledgments

We want to thank Brad Rikke for his contributions to this project. The project was supported by funds from the NIAAA and the University of Colorado Boulder, from a gift to the UCB from TEJ, and from the NICHD training grant.

References

  1. Bennet B (2000) Congenic strains developed for alcohol-and drug-related phenotypes. Pharmacol Biochem Behav 67:671–681CrossRefGoogle Scholar
  2. Bennett B, Beeson M, Gordon L, Johnson TE (2002) Reciprocal congenics defining individual quantitative trait loci for sedative/hypnotic sensitivity to ethanol. Alcohol Clin Exp Res 26:149–157CrossRefPubMedGoogle Scholar
  3. Bennett B, Carosone-Link P, Zahniser NR, Johnson TE (2006) Confirmation and fine mapping of ethanol sensitivity QTLs, and candidate gene testing in the LXS recombinant inbred mice. J Pharmacol Exp Ther 319:299–307CrossRefPubMedGoogle Scholar
  4. Bennett B, Carosone-Link P, Beeson M, Gordon L, Phares-Zook N, Johnson TE (2008) Genetic dissection of quantitative trait loci for ethanol sensitivity in long- and short-sleep mice. Genes Brain Behav 7:659–668CrossRefPubMedGoogle Scholar
  5. Finch CE (1990) Longevity, senescence, and the genome. The University of Chicago Press, ChicagoGoogle Scholar
  6. Forster MJ, Morris P, Sohal RS (2003) Genotype and age influence the effect of caloric intake on mortality in mice. FASEB J 17:690–692PubMedCentralPubMedGoogle Scholar
  7. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider NL (1990) Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mech Ageing Dev 55:69-87CrossRefPubMedGoogle Scholar
  8. Harper JM, Leathers CS, Austad SN (2006) Does caloric restriction extend life in wild mice? Aging Cell 5:441–449Google Scholar
  9. Kenyon CJ (2010) The genetics of aging. Nature 464:504–512CrossRefPubMedGoogle Scholar
  10. Lee C, Klopp RG, Weindruch R, Prolla TA (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285:1390–1393CrossRefPubMedGoogle Scholar
  11. Liao CY, Rikke BA, Johnson TE, Diaz V, Nelson JF (2010) Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell 9:92–95CrossRefPubMedCentralPubMedGoogle Scholar
  12. Liao CY, Rikke BA, Johnson TE, Gelfond JA, Diaz V, Nelson JF (2011) Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell 10:629–39CrossRefPubMedCentralPubMedGoogle Scholar
  13. Liao CY, Johnson TE, Nelson JF (2013) Genetic variation in responses to DR—an unbiased tool for hypothesis testing. Exp Gerontol 48:1025–9CrossRefPubMedCentralPubMedGoogle Scholar
  14. Masoro EJ (2005) Overview of caloric restriction and ageing. Mech Ageing Dev 126:913–922CrossRefPubMedGoogle Scholar
  15. McCay CM, Crowell MF, Maynard LA (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 10:63–79Google Scholar
  16. McCay CM, Maynard LA, Sperling G, and Barnes LL (1939) Retarded growth, life span, ultimate body size and age changes in the albino rat after feeding diets restricted in calories. J Nutr 18:1–13Google Scholar
  17. Nutrient Requirements of Laboratory Animals (1995) Fourth Revised Edition, Washington, DC: The National Academy Press 80-102Google Scholar
  18. Rasband WS (1997–2011) ImageJ. U.S. National Institutes of Health, Bethesda, Maryland, USA, http://imagej.nih.gov/ij/
  19. Rikke BA, Johnson TE (1998) Towards the cloning of genes underlying murine QTLs. Mamm Genome 9:963–968CrossRefPubMedGoogle Scholar
  20. Rikke BA, Johnson TE (2007) Physiological genetics of dietary restriction: uncoupling the body temperature and body weight responses. Am J Physiol Regul Integr Comp Physiol 293:R1522–R1527CrossRefPubMedGoogle Scholar
  21. Rikke BA, Yerg JE 3rd, Battaglia ME, Nagy TR, Allison DB, Johnson TE (2003) Strain variation in the response of body temperature to dietary restriction. Mech Aging Dev 124:663–78CrossRefPubMedGoogle Scholar
  22. Rikke BA, Battaglia ME, Allison DB, Johnson TE (2006) Murine weight loss exhibits significant genetic variation during dietary restriction. Physiol Genomics 27:122–130CrossRefPubMedGoogle Scholar
  23. Rikke BA, Liao CY, McQueen MB, Nelson JF, Johnson TE (2010) Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension. Exp Gerontol 45:691–701CrossRefPubMedCentralPubMedGoogle Scholar
  24. Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H (1994) Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74:121–133CrossRefPubMedGoogle Scholar
  25. Swindell WR (2011) Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan. Ageing Res Rev 11:254–270CrossRefPubMedCentralPubMedGoogle Scholar
  26. Williams RW, Bennett B, Lu L, Gu J, DeFries JC, Carosone-Link PJ, Rikke BA, Belknap JK, Johnson TE (2004) Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis. Mamm Genome 15:637–647Google Scholar
  27. Weindruch R, Walford RL (1988) The retardation of aging and disease by dietary restriction. C.C. Thomas, SpringfieldGoogle Scholar

Copyright information

© American Aging Association 2015

Authors and Affiliations

  • Breanne L. Newell
    • 1
    • 2
    Email author
  • Katerina Kechris
    • 3
  • Matt B. McQueen
    • 1
    • 2
  • Thomas E. Johnson
    • 1
    • 2
  1. 1.Institute for Behavioral GeneticsUniversity of ColoradoBoulderUSA
  2. 2.Department of Integrative PhysiologyUniversity of ColoradoBoulderUSA
  3. 3.Department of Biostatistics and Informatics, Colorado School of Public HealthUniversity of Colorado DenverAuroraUSA

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