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. 1999 Jun;152(2):699–711. doi: 10.1093/genetics/152.2.699

Identification of quantitative trait loci influencing traits related to energy balance in selection and inbred lines of mice.

D E Moody 1, D Pomp 1, M K Nielsen 1, L D Van Vleck 1
PMCID: PMC1460635  PMID: 10353911

Abstract

Energy balance is a complex trait with relevance to the study of human obesity and maintenance energy requirements of livestock. The objective of this study was to identify, using unique mouse models, quantitative trait loci (QTL) influencing traits that contribute to variation in energy balance. Two F2 resource populations were created from lines of mice differing in heat loss measured by direct calorimetry as an indicator of energy expenditure. The HB F2 resource population originated from a cross between a noninbred line selected for high heat loss and an inbred line with low heat loss. Evidence for significant QTL influencing heat loss was found on chromosomes 1, 2, 3, and 7. Significant QTL influencing body weight and percentage gonadal fat, brown fat, liver, and heart were also identified. The LH F2 resource population originated from noninbred lines of mice that had undergone divergent selection for heat loss. Chromosomes 1 and 3 were evaluated. The QTL for heat loss identified on chromosome 1 in the HB population was confirmed in the LH population, although the effect was smaller. The presence of a QTL influencing 6-wk weight was also confirmed. Suggestive evidence for additional QTL influencing heat loss, percentage subcutaneous fat, and percentage heart was found for chromosome 1.

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Selected References

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  1. Andersson L., Haley C. S., Ellegren H., Knott S. A., Johansson M., Andersson K., Andersson-Eklund L., Edfors-Lilja I., Fredholm M., Hansson I. Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science. 1994 Mar 25;263(5154):1771–1774. doi: 10.1126/science.8134840. [DOI] [PubMed] [Google Scholar]
  2. Boss O., Samec S., Paoloni-Giacobino A., Rossier C., Dulloo A., Seydoux J., Muzzin P., Giacobino J. P. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett. 1997 May 12;408(1):39–42. doi: 10.1016/s0014-5793(97)00384-0. [DOI] [PubMed] [Google Scholar]
  3. Bouchard C., Pérusse L., Chagnon Y. C., Warden C., Ricquier D. Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans. Hum Mol Genet. 1997 Oct;6(11):1887–1889. doi: 10.1093/hmg/6.11.1887. [DOI] [PubMed] [Google Scholar]
  4. Cassard-Doulcier A. M., Larose M., Matamala J. C., Champigny O., Bouillaud F., Ricquier D. In vitro interactions between nuclear proteins and uncoupling protein gene promoter reveal several putative transactivating factors including Ets1, retinoid X receptor, thyroid hormone receptor, and a CACCC box-binding protein. J Biol Chem. 1994 Sep 30;269(39):24335–24342. [PubMed] [Google Scholar]
  5. Churchill G. A., Doerge R. W. Empirical threshold values for quantitative trait mapping. Genetics. 1994 Nov;138(3):963–971. doi: 10.1093/genetics/138.3.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Enerbäck S., Jacobsson A., Simpson E. M., Guerra C., Yamashita H., Harper M. E., Kozak L. P. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997 May 1;387(6628):90–94. doi: 10.1038/387090a0. [DOI] [PubMed] [Google Scholar]
  7. Fleury C., Neverova M., Collins S., Raimbault S., Champigny O., Levi-Meyrueis C., Bouillaud F., Seldin M. F., Surwit R. S., Ricquier D. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet. 1997 Mar;15(3):269–272. doi: 10.1038/ng0397-269. [DOI] [PubMed] [Google Scholar]
  8. Gené-Badia J. Labour's health policy is having paradoxical effect in Iberian countries. BMJ. 1999 Feb 13;318(7181):466–467. [PMC free article] [PubMed] [Google Scholar]
  9. Haley C. S., Knott S. A. A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity (Edinb) 1992 Oct;69(4):315–324. doi: 10.1038/hdy.1992.131. [DOI] [PubMed] [Google Scholar]
  10. Himms-Hagen J. Role of thermogenesis in the regulation of energy balance in relation to obesity. Can J Physiol Pharmacol. 1989 Apr;67(4):394–401. doi: 10.1139/y89-063. [DOI] [PubMed] [Google Scholar]
  11. Jones L. D., Nielsen M. K., Britton R. A. Genetic variation in liver mass, body mass, and liver:body mass in mice. J Anim Sci. 1992 Oct;70(10):2999–3006. doi: 10.2527/1992.70102999x. [DOI] [PubMed] [Google Scholar]
  12. Lander E. S., Botstein D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989 Jan;121(1):185–199. doi: 10.1093/genetics/121.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  14. Moody D. E., Pomp D., Nielsen M. K. Variability in metabolic rate, feed intake and fatness among selection and inbred lines of mice. Genet Res. 1997 Dec;70(3):225–235. doi: 10.1017/s0016672397003017. [DOI] [PubMed] [Google Scholar]
  15. Nakamura M., Aoki Y., Hirano D. Cloning and functional expression of a cDNA encoding a mouse type 2 neuropeptide Y receptor. Biochim Biophys Acta. 1996 Oct 23;1284(2):134–137. doi: 10.1016/s0005-2736(96)00166-6. [DOI] [PubMed] [Google Scholar]
  16. Naylor S. L., Sakaguchi A. Y., McDonald L., Todd S., Lalley P. A., Shows T. B., Chin W. W. Mapping thyrotropin beta subunit gene in man and mouse. Somat Cell Mol Genet. 1986 May;12(3):307–311. doi: 10.1007/BF01570791. [DOI] [PubMed] [Google Scholar]
  17. Nielsen M. K., Freking B. A., Jones L. D., Nelson S. M., Vorderstrasse T. L., Hussey B. A. Divergent selection for heat loss in mice: II. Correlated responses in feed intake, body mass, body composition, and number born through fifteen generations. J Anim Sci. 1997 Jun;75(6):1469–1476. doi: 10.2527/1997.7561469x. [DOI] [PubMed] [Google Scholar]
  18. Nielsen M. K., Jones L. D., Freking B. A., DeShazer J. A. Divergent selection for heat loss in mice: I. Selection applied and direct response through fifteen generations. J Anim Sci. 1997 Jun;75(6):1461–1468. doi: 10.2527/1997.7561461x. [DOI] [PubMed] [Google Scholar]
  19. Norman R. A., Tataranni P. A., Pratley R., Thompson D. B., Hanson R. L., Prochazka M., Baier L., Ehm M. G., Sakul H., Foroud T. Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. Am J Hum Genet. 1998 Mar;62(3):659–668. doi: 10.1086/301758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pomp D. Genetic dissection of obesity in polygenic animal models. Behav Genet. 1997 Jul;27(4):285–306. doi: 10.1023/a:1025631813018. [DOI] [PubMed] [Google Scholar]
  21. Pomp D., Nielsen M. K. Quantitative genetics of energy balance--lessons from animal models. Obes Res. 1999 Jan;7(1):106–110. doi: 10.1002/j.1550-8528.1999.tb00397.x. [DOI] [PubMed] [Google Scholar]
  22. Ravussin E., Lillioja S., Knowler W. C., Christin L., Freymond D., Abbott W. G., Boyce V., Howard B. V., Bogardus C. Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med. 1988 Feb 25;318(8):467–472. doi: 10.1056/NEJM198802253180802. [DOI] [PubMed] [Google Scholar]
  23. Rice T., Tremblay A., Dériaz O., Pérusse L., Rao D. C., Bouchard C. Genetic pleiotropy for resting metabolic rate with fat-free mass and fat mass: the Québec Family Study. Obes Res. 1996 Mar;4(2):125–131. doi: 10.1002/j.1550-8528.1996.tb00524.x. [DOI] [PubMed] [Google Scholar]
  24. Roberts S. B., Savage J., Coward W. A., Chew B., Lucas A. Energy expenditure and intake in infants born to lean and overweight mothers. N Engl J Med. 1988 Feb 25;318(8):461–466. doi: 10.1056/NEJM198802253180801. [DOI] [PubMed] [Google Scholar]
  25. Saltzman E., Roberts S. B. The role of energy expenditure in energy regulation: findings from a decade of research. Nutr Rev. 1995 Aug;53(8):209–220. doi: 10.1111/j.1753-4887.1995.tb01554.x. [DOI] [PubMed] [Google Scholar]
  26. Thomas S. A., Palmiter R. D. Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature. 1997 May 1;387(6628):94–97. doi: 10.1038/387094a0. [DOI] [PubMed] [Google Scholar]
  27. Vidal-Puig A., Solanes G., Grujic D., Flier J. S., Lowell B. B. UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun. 1997 Jun 9;235(1):79–82. doi: 10.1006/bbrc.1997.6740. [DOI] [PubMed] [Google Scholar]
  28. Warden C. H., Fisler J. S., Shoemaker S. M., Wen P. Z., Svenson K. L., Pace M. J., Lusis A. J. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest. 1995 Apr;95(4):1545–1552. doi: 10.1172/JCI117827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woods S. C., Seeley R. J., Porte D., Jr, Schwartz M. W. Signals that regulate food intake and energy homeostasis. Science. 1998 May 29;280(5368):1378–1383. doi: 10.1126/science.280.5368.1378. [DOI] [PubMed] [Google Scholar]
  30. Zeng Z. B. Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10972–10976. doi: 10.1073/pnas.90.23.10972. [DOI] [PMC free article] [PubMed] [Google Scholar]

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