Mammalian Genome

, 22:530 | Cite as

Genetic determinants for intramuscular fat content and water-holding capacity in mice selected for high muscle mass

  • Stefan Kärst
  • Riyan Cheng
  • Armin O. Schmitt
  • Hyuna Yang
  • Fernando Pardo Manuel de Villena
  • Abraham A. Palmer
  • Gudrun A. Brockmann


Intramuscular fat content and water-holding capacity are important traits in livestock as they influence meat quality, nutritive value of the muscle, and animal health. As a model for livestock, two inbred lines of the Berlin Muscle Mouse population, which had been long-term selected for high muscle mass, were used to identify genomic regions affecting intramuscular fat content and water-holding capacity. The intramuscular fat content of the Musculus longissimus was on average 1.4 times higher in BMMI806 than in BMMI816 mice. This was accompanied by a 1.5 times lower water-holding capacity of the Musculus quadriceps in BMMI816 mice. Linkage analyses with 332 G3 animals of reciprocal crosses between these two lines revealed quantitative trait loci for intramuscular fat content on chromosome 7 and for water-holding capacity on chromosome 2. In part, the identified loci coincide with syntenic regions in pigs in which genetic effects for the same traits were found. Therefore, these muscle-weight-selected mouse lines and the produced intercross populations are valuable genetic resources to identify genes that could also contribute to meat quality in other species.


  1. Armstrong RB, Phelps RO (1984) Muscle fiber type composition of the rat hindlimb. Am J Anat 171:259–272PubMedCrossRefGoogle Scholar
  2. Barham D, Trinder P (1972) An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst 97:142–145PubMedCrossRefGoogle Scholar
  3. Bee G, Anderson AL, Lonergan SM, Huff-Lonergan E (2007) Rate and extent of pH decline affect proteolysis of cytoskeletal proteins and water-holding capacity in pork. Meat Sci 76:359–365CrossRefGoogle Scholar
  4. Birney E, Andrews TD, Bevan P, Caccamo M, Chen Y, Clarke L, Coates G, Cuff J, Curwen V, Cutts T, Down T, Eyras E, Fernandez-Suarez XM, Gane P, Gibbins B, Gilbert J, Hammond M, Hotz HR, Iyer V, Jekosch K, Kahari A, Kasprzyk A, Keefe D, Keenan S, Lehvaslaiho H, McVicker G, Melsopp C, Meidl P, Mongin E, Pettett R, Potter S, Proctor G, Rae M, Searle S, Slater G, Smedley D, Smith J, Spooner W, Stabenau A, Stalker J, Storey R, Ureta-Vidal A, Woodwark KC, Cameron G, Durbin R, Cox A, Hubbard T, Clamp M (2004) An overview of Ensembl. Genome Res 14:925–928PubMedCrossRefGoogle Scholar
  5. Brockmann GA, Bevova MR (2002) Using mouse models to dissect the genetics of obesity. Trends Genet 18:367–376PubMedCrossRefGoogle Scholar
  6. Brockmann GA, Karatayli E, Haley CS, Renne U, Rottmann OJ, Karle S (2004) QTLs for pre- and postweaning body weight and body composition in selected mice. Mamm Genome 15:593–609PubMedCrossRefGoogle Scholar
  7. Broman KW, Wu H, Sen S, Churchill GA (2003) R/qtl: QTL mapping in experimental crosses. Bioinformatics 19:889–890PubMedCrossRefGoogle Scholar
  8. Cannata S, Engle TE, Moeller SJ, Zerby HN, Radunz AE, Green MD, Bass PD, Belk KE (2010) Effect of visual marbling on sensory properties and quality traits of pork loin. Meat Sci 85(3):428–434PubMedCrossRefGoogle Scholar
  9. Chadt A, Leicht K, Deshmukh A, Jiang LQ, Scherneck S, Bernhardt U, Dreja T, Vogel H, Schmolz K, Kluge R, Zierath JR, Hultschig C, Hoeben RC, Schurmann A, Joost HG, Al-Hasani H (2008) Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 40:1354–1359PubMedCrossRefGoogle Scholar
  10. Cheng R, Lim JE, Samocha KE, Sokoloff G, Abney M, Skol AD, Palmer AA (2010) Genome-wide association studies and the problem of relatedness among advanced intercross lines and other highly recombinant populations. Genetics 185:1033–1044PubMedCrossRefGoogle Scholar
  11. Choe JH, Choi YM, Lee SH, Shin HG, Ryu YC, Hong KC, Kim BC (2008) The relation between glycogen, lactate content and muscle fiber type composition, and their influence on postmortem glycolytic rate and pork quality. Meat Sci 80:355–362CrossRefGoogle Scholar
  12. Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138:963–971PubMedGoogle Scholar
  13. Cox A, Ackert-Bicknell CL, Dumont BL, Ding Y, Bell JT, Brockmann GA, Wergedal JE, Bult C, Paigen B, Flint J, Tsaih SW, Churchill GA, Broman KW (2009) A new standard genetic map for the laboratory mouse. Genetics 182:1335–1344PubMedCrossRefGoogle Scholar
  14. Darvasi A, Soller M (1995) Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141:1199–1207PubMedGoogle Scholar
  15. de Koning DJ, Janss LL, Rattink AP, van Oers PA, de Vries BJ, Groenen MA, van der Poel JJ, de Groot PN, Brascamp EW, van Arendonk JA (1999) Detection of quantitative trait loci for backfat thickness and intramuscular fat content in pigs (Sus scrofa). Genetics 152:1679–1690PubMedGoogle Scholar
  16. de Koning DJ, Rattink AP, Harlizius B, van Arendonk JA, Brascamp EW, Groenen MA (2000) Genome-wide scan for body composition in pigs reveals important role of imprinting. Proc Natl Acad Sci USA 97:7947–7950PubMedCrossRefGoogle Scholar
  17. Dragos-Wendrich M, Sternstein I, Brunsch C, Moser G, Bartenschlager H, Reiner G, Geldermann H (2003) Linkage and QTL mapping for Sus scrofa chromosome 14. J Anim Breed Genet 120:111–118CrossRefGoogle Scholar
  18. Eaton S (2002) Control of mitochondrial [beta]-oxidation flux. Progr Lipid Res 41:197–239CrossRefGoogle Scholar
  19. Ebeling P, Essen-Gustavsson B, Tuominen JA, Koivisto VA (1998) Intramuscular triglyceride content is increased in IDDM. Diabetologia 41:111–115PubMedCrossRefGoogle Scholar
  20. Fernandez X, Monin G, Talmant A, Mourot J, Lebret B (1999) Influence of intramuscular fat content on the quality of pig meat-1. Composition of the lipid fraction and sensory characteristics of m. longissimus lumborum. Meat Sci 53:59–65CrossRefGoogle Scholar
  21. Fujii J, Otsu K, Zorzato F, de Leon S, Khanna VK, Weiler JE, O’Brien PJ, MacLennan DH (1991) Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253:448–451PubMedCrossRefGoogle Scholar
  22. Hamalainen N, Pette D (1993) The histochemical profiles of fast fiber types IIB, IID, and IIA in skeletal muscles of mouse, rat, and rabbit. J Histochem Cytochem 41:733–743PubMedCrossRefGoogle Scholar
  23. Hansson O, Donsmark M, Ling C, Nevsten P, Danfelter M, Andersen JL, Galbo H, Holm C (2005) Transcriptome and proteome analysis of soleus muscle of hormone-sensitive lipase-null mice. J Lipid Res 46:2614–2623PubMedCrossRefGoogle Scholar
  24. Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE (2006) Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs. FASEB J 20:1855–1864PubMedCrossRefGoogle Scholar
  25. Kaerst S, Schmitt A, Brockmann G (2010) A novel method for measuring of fat content in low-weight tissue: a NMR study. WebmedCentral OBESITY 2010;1(12):WMC001368.
  26. Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846PubMedCrossRefGoogle Scholar
  27. Knott SA, Marklund L, Haley CS, Andersson K, Davies W, Ellegren H, Fredholm M, Hansson I, Hoyheim B, Lundstrom K, Moller M, Andersson L (1998) Multiple marker mapping of quantitative trait loci in a cross between outbred wild boar and large white pigs. Genetics 149:1069–1080PubMedGoogle Scholar
  28. Lambe NR, Macfarlane JM, Richardson RI, Matika O, Haresign W, Bünger L (2010) The effect of the Texel muscling QTL (TM-QTL) on meat quality traits in crossbred lambs. Meat Sci 85:684–690PubMedCrossRefGoogle Scholar
  29. Leavens KF, Easton RM, Shulman GI, Previs SF, Birnbaum MJ (2009) Akt2 is required for hepatic lipid accumulation in models of insulin resistance. Cell Metab 10:405–418PubMedCrossRefGoogle Scholar
  30. Lionikas A, Blizard DA, Gerhard GS, Vandenbergh DJ, Stout JT, Vogler GP, McClearn GE, Larsson L (2005) Genetic determinants of weight of fast- and slow-twitch skeletal muscle in 500-day-old mice of the C57BL/6J and DBA/2J lineage. Physiol Genom 21:184–192CrossRefGoogle Scholar
  31. Lionikas A, Blizard D, Vandenbergh D, Stout J, Vogler G, McClearn G, Larsson L (2006) Genetic determinants of weight of fast- and slow-twitch skeletal muscles in old mice. Mamm Genome 17:615–628PubMedCrossRefGoogle Scholar
  32. Liu G, Kim JJ, Jonas E, Wimmers K, Ponsuksili S, Murani E, Phatsara C, Tholen E, Juengst H, Tesfaye D, Chen JL, Schellander K (2008) Combined line-cross and half-sib QTL analysis in Duroc-Pietrain population. Mamm Genome 19:429–438PubMedCrossRefGoogle Scholar
  33. Ludden PA, Kucuk O, Rule DC, Hess BW (2009) Growth and carcass fatty acid composition of beef steers fed soybean oil for increasing duration before slaughter. Meat Sci 82:185–192CrossRefGoogle Scholar
  34. Malek M, Dekkers JC, Lee HK, Baas TJ, Prusa K, Huff-Lonergan E, Rothschild MF (2001) A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. II. Meat and muscle composition. Mamm Genome 12:637–645PubMedCrossRefGoogle Scholar
  35. Mott R (2005) Perl script “”.
  36. Neuschl C, Hantschel C, Wagener A, Schmitt AO, Illig T, Brockmann GA (2010) A unique genetic defect on chromosome 3 is responsible for juvenile obesity in the Berlin Fat Mouse. Int J Obes (Lond) 34(12):1706–1714CrossRefGoogle Scholar
  37. Ochoa O, Shireman PK, McManus LM (2006) Altered inflammation increases intramuscular fat accumulation and impairs skeletal muscle regeneration following ischemic injury in CCR2−/− mice. J Am Coll Surg 203:S101CrossRefGoogle Scholar
  38. Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46:983–988PubMedCrossRefGoogle Scholar
  39. Paszek AA, Wilkie PJ, Flickinger GH, Miller LM, Louis CF, Rohrer GA, Alexander LJ, Beattie CW, Schook LB (2001) Interval mapping of carcass and meat quality traits in a divergent swine cross. Anim Biotechnol 12:155–165PubMedCrossRefGoogle Scholar
  40. Phillips DIW, Caddy S, Ilic V, Fielding BA, Frayn KN, Borthwick AC, Taylor R (1996) Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism 45:947–950PubMedCrossRefGoogle Scholar
  41. Ponsuksili S, Jonas E, Murani E, Phatsara C, Srikanchai T, Walz C, Schwerin M, Schellander K, Wimmers K (2008) Trait correlated expression combined with expression QTL analysis reveals biological pathways and candidate genes affecting water holding capacity of muscle. BMC Genom 9:367CrossRefGoogle Scholar
  42. Powell DJ, Turban S, Gray A, Hajduch E, Hundal HS (2004) Intracellular ceramide synthesis and protein kinase Czeta activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem J 382:619–629PubMedCrossRefGoogle Scholar
  43. Rehfeldt C, Renne U, Sawitzky M, Binder G, Hoeflich A (2010) Increased fat mass, decreased myofiber size, and a shift to glycolytic muscle metabolism in adolescent male transgenic mice overexpressing IGFBP-2. Am J Physiol Endocrinol Metab 299:E287–E298PubMedGoogle Scholar
  44. Rohrer GA, Alexander LJ, Hu Z, Smith TP, Keele JW, Beattie CW (1996) A comprehensive map of the porcine genome. Genome Res 6:371–391PubMedCrossRefGoogle Scholar
  45. Schmitt AO, Al-Hasani H, Cheverud JM, Pomp D, Bunger L, Brockmann GA (2007) Fine mapping of mouse QTLs for fatness using SNP data. OMICS 11:341–350PubMedCrossRefGoogle Scholar
  46. Schmitt A, Bortfeldt R, Neuschl C, Brockmann G (2009) RandoMate: a program for the generation of random mating schemes for small laboratory animals. Mamm Genome 20:321–325PubMedCrossRefGoogle Scholar
  47. Schmitz-Peiffer C (2000) Signalling aspects of insulin resistance in skeletal muscle: mechanisms induced by lipid oversupply. Cell Signal 12:583–594PubMedCrossRefGoogle Scholar
  48. Schwab CR, Mote BE, Du ZQ, Amoako R, Baas TJ, Rothschild MF (2009) An evaluation of four candidate genes for use in selection programmes aimed at increased intramuscular fat in Duroc swine. J Anim Breed Genet 126:228–236PubMedCrossRefGoogle Scholar
  49. Szabo G, Dallmann G, Muller G, Patthy L, Soller M, Varga L (1998) A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice. Mamm Genome 9:671–672PubMedCrossRefGoogle Scholar
  50. Tanomura H, Miyake T, Taniguchi Y, Manabe N, Kose H, Matsumoto K, Yamada T, Sasaki Y (2002) Detection of a quantitative trait locus for intramuscular fat accumulation using the OLETF rat. J Vet Med Sci 64:45–50PubMedCrossRefGoogle Scholar
  51. Tinsley FC, Taicher GZ, Heiman ML (2004) Evaluation of a quantitative magnetic resonance method for mouse whole body composition analysis. Obesity 12:150–160CrossRefGoogle Scholar
  52. Tyra M, Ropka-Molik K, Eckert R, Piórkowska K, Oczkowicz M (2010) H-FABP and LEPR gene expression profile in skeletal muscles and liver during ontogenesis in various breeds of pigs. Domest Anim Endocrinol 40(3):147–154PubMedCrossRefGoogle Scholar
  53. Underwood KR, Tong J, Zhu MJ, Shen QW, Means WJ, Ford SP, Paisley SI, Hess BW, Du M (2007) Relationship between kinase phosphorylation, muscle fiber typing, and glycogen accumulation in longissimus muscle of beef cattle with high and low intramuscular fat. J Agric Food Chem 55:9698–9703PubMedCrossRefGoogle Scholar
  54. Valdar WJ, Flint J, Mott R (2003) QTL fine-mapping with recombinant-inbred heterogeneous stocks and in vitro heterogeneous stocks. Mamm Genome 14:830–838PubMedCrossRefGoogle Scholar
  55. Varga L, Szabo G, Darvasi A, Muller G, Sass M, Soller M (1997) Inheritance and mapping of Compact (Cmpt), a new mutation causing hypermuscularity in mice. Genetics 147:755–764PubMedGoogle Scholar
  56. Wimmers K, Murani E, Ponsuksili S (2010) Functional genomics and genetical genomics approaches towards elucidating networks of genes affecting meat performance in pigs. Brief Funct Genom 9:251–258CrossRefGoogle Scholar
  57. Wood JD, Richardson RI, Nute GR, Fisher AV, Campo MM, Kasapidou E, Sheard PR, Enser M (2004) Effects of fatty acids on meat quality: a review. Meat Sci 66:21–32CrossRefGoogle Scholar
  58. Yang H, Ding Y, Hutchins LN, Szatkiewicz J, Bell TA, Paigen BJ, Graber JH, de Villena FP, Churchill GA (2009) A customized and versatile high-density genotyping array for the mouse. Nat Methods 6:663–666PubMedCrossRefGoogle Scholar
  59. Yaspelkis BB, Singh MK, Krisan AD, Collins DE, Kwong CC, Bernard JR, Crain AM (2004) Chronic leptin treatment enhances insulin-stimulated glucose disposal in skeletal muscle of high-fat fed rodents. Life Sci 74:1801–1816PubMedCrossRefGoogle Scholar
  60. Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI (2002) Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 277:50230–50236PubMedCrossRefGoogle Scholar
  61. Zhang WG, Lonergan SM, Gardner MA, Huff-Lonergan E (2006) Contribution of postmortem changes of integrin, desmin and [mu]-calpain to variation in water holding capacity of pork. Meat Sci 74:578–585CrossRefGoogle Scholar
  62. Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI (2007) Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci USA 104:17075–17080PubMedCrossRefGoogle Scholar
  63. Zhao SM, Ren LJ, Guo L, Cheng ML, Zhang X, Ge CR, Gao SZ (2010) Muscle lipid metabolism gene expression in pigs with different H-FABP genotypes. Livestock Sci 128:101–107CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Stefan Kärst
    • 1
  • Riyan Cheng
    • 2
  • Armin O. Schmitt
    • 1
    • 4
  • Hyuna Yang
    • 3
  • Fernando Pardo Manuel de Villena
    • 3
  • Abraham A. Palmer
    • 2
  • Gudrun A. Brockmann
    • 1
  1. 1.Department for Crop and Animal SciencesHumboldt-Universität zu BerlinBerlinGermany
  2. 2.Department of Human GeneticsUniversity of ChicagoChicagoUSA
  3. 3.Department of Genetics, School of MedicineUniversity of North CarolinaChapel HillUSA
  4. 4.Faculty of Science and TechnologyUniversitätsplatz 5—piazza UniversitàBozen-BolzanoItaly

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