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A growth QTL (Pbwg1) region of mouse chromosome 2 contains closely linked loci affecting growth and body composition

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Abstract

Previous QTL studies have identified 24 QTLs for body weight and growth from 3 to 10 weeks after birth in an intersubspecific backcross mouse population between C57BL/6J and wild Mus musculus castaneus that has 60% of the body size of C57BL/6J. The castaneus allele at the most potent QTL (Pbwg1) on proximal chromosome 2 retards growth. In this study we have developed a congenic strain with a 44.1-Mb interval containing the castaneus allele at Pbwg1 by recurrent backcrossing to C57BL/6J. The congenic mouse developed was characterized by significantly higher body weight gain between 1 and 3 weeks of age and lower weight of white fat pads at 10 weeks of age than C57BL/6J. However, no clear difference in body weight at 1–10 weeks of age was observed between congenic and C57BL/6J strains. QTL analysis with 269 F2 mice between the two strains did not identify any QTLs for body weight at 1, 3, 6, and 10 weeks of age, but it discovered eight closely linked QTLs affecting body weight gain from 1 to 3 weeks of age, lean body weight, weight of white fat pads, and body length within the Pbwg1 region. The castaneus alleles at all fat pad QTLs reduced the phenotypes, whereas at the remaining growth and body composition QTLs, they increased the trait values. These results illustrate that Pbwg1, which initially appeared to be a single locus, was resolved into several loci with opposite effects on the composition traits of overall body weight. This gives a reason for the loss of the Pbwg1 effect found in the original backcross population.

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References

  • Brockmann GA, Karatayli E, Haley CS, Renne U, Rottmann OJ, et al. (2004) QTLs for pre- and postweaning body weight and body composition in selected mice. Mamm Genome 15:593–609

    Article  PubMed  Google Scholar 

  • Christians JK, Keightley PD (2004) Fine mapping of a murine growth locus to a 1.4-cM region and resolution of linked QTL. Mamm Genome 15:482–491

    Article  PubMed  CAS  Google Scholar 

  • Christians JK, Hoeflich A, Keightley PD (2006) PAPPA2, an enzyme that cleaves an insulin-like growth-factor-binding protein, is a candidate gene for a quantitative trait locus affecting body size in mice. Genetics 173:1547–1553

    Article  PubMed  CAS  Google Scholar 

  • Corva PM, Horvat S, Medrano JF (2001) Quantitative trait loci affecting growth in high growth (hg) mice. Mamm Genome 12:284–290

    Article  PubMed  CAS  Google Scholar 

  • Estrada-Smith D, Castellani LW, Wong H, Wen P-Z, Chui A, et al. (2004) Dissection of multigenic obesity traits in congenic mouse strains. Mamm Genome 15:14–22

    Article  PubMed  CAS  Google Scholar 

  • Farber CR, Corva PM, Medrano JF (2006) Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains. BMC Genomics 7:102

    Article  PubMed  CAS  Google Scholar 

  • Festing MWF (1996) Origins and characteristics of inbred strains of mice. In Lyon MF, Rastan S, Brown SDM, eds. Genetic Variants and Strains of the Laboratory Mouse, vol 2, 3rd ed. New York: Oxford University Press, pp 1537–1576

    Google Scholar 

  • Fishman L, Kelly AJ, Willis JH (2002) Minor quantitative trait loci underlie floral traits associated with mating system divergence in Mimulus. Evolution 56:2138–2155

    PubMed  Google Scholar 

  • Flint J, Valdar W, Shifman S, Mott R (2005) Strategies for mapping and cloning quantitative trait genes in rodents. Nat Rev Genet 6:271–286

    Article  PubMed  CAS  Google Scholar 

  • Haley CS, Knott SA (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69:315–324

    PubMed  CAS  Google Scholar 

  • Horvat S, Bunger L, Falconer VM, Mackay P, Law A, et al. (2000) Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm Genome 11:2–7

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa A, Namikawa T (2004) Mapping major quantitative trait loci for postnatal growth in an intersubspecific backcross between C57BL/6J and Philippine wild mice by using principal component analysis. Genes Genet Syst 79:27–39

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa A, Matsuda Y, Namikawa T (2000) Detection of quantitative trait loci for body weight at 10 weeks from Philippine wild mice. Mamm Genome 11:824–830

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa A, Hatada S, Nagamine Y, Namikawa T (2005) Further mapping of quantitative trait loci for postnatal growth in an intersubspecific backcross of wild Mus musculus castaneus and C57BL/6J mice. Genet Res 85:127–137

    Article  PubMed  CAS  Google Scholar 

  • Jiang C, Zeng Z-B (1995) Multiple trait analysis of genetic mapping for quantitative trait loci. Genetics 140:1111–1127

    PubMed  CAS  Google Scholar 

  • Kao C-H, Zeng Z-B, Teasdale RD (1999) Multiple interval mapping for quantitative trait loci. Genetics 152:1203–1216

    PubMed  CAS  Google Scholar 

  • Kenney-Hunt JP, Vaughn TT, Pletscher LS, Peripato A, Routman E, et al. (2006) Quantitative trait loci for body size components in mice. Mamm Genome 17:526–537

    Article  PubMed  Google Scholar 

  • Lander ES, Botstein D (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:184–199

    Google Scholar 

  • Lang DH, Sharkey NA, Lionikas A, Mack HA, Larsson L, et al. (2005) Adjusting data to body size: a comparison of methods as applied to quantitative trait loci analysis of musculoskeletal phenotypes. J Bone Miner Res 20:748–757

    Article  PubMed  Google Scholar 

  • Lionikas A, Blizard DA, Vandenbergh DJ, Glover MG, Stout JT, et al. (2003) Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage. Physiol Genomics 16:141–152

    Article  PubMed  CAS  Google Scholar 

  • Lionikas A, Blizard DA, Gerhard GS, Vandenbergh DJ, Stout JT, et al. (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 Genomics 21:184–192

    Article  PubMed  CAS  Google Scholar 

  • Manly KF, Cudmore Jr RH, Meer JM (2001) Map Manager QTX, cross-platform software for genetic mapping. Mamm Genome 12:930–932

    Article  PubMed  CAS  Google Scholar 

  • Masinde GL, Li X, Gu W, Davidson H, Hamilton-Ulland M, et al. (2002) Quantitative trait loci (QTL) for lean body mass and body length in MRL/MPJ and SJL/J F2 mice. Funct Integr Genomics 2:98–104

    Article  PubMed  CAS  Google Scholar 

  • Mehrabian MM, Wen P-Z, Fisler J, Davis RC, Lusis AJ (1998) Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model. J Clin Invest 101:2485–2496

    Article  PubMed  CAS  Google Scholar 

  • Mizutani S, Gomi H. Hirayama I, Izumi T (2006) Chromosome 2 locus Nidd5 has a potent effect on adiposity in the TSOD mouse. Mamm Genome 17:375–384

    Article  PubMed  CAS  Google Scholar 

  • Oliver F, Christians JK, Liu X, Rhind S, Verma V, et al. (2005) Regulatory variation at glypican-3 underlies a major growth QTL in mice. PLoS Biol 3:872–877

    Article  CAS  Google Scholar 

  • Peters LL, Zhang W, Lambert AJ, Brugnara C, Churchill GA, et al. (2005) Quantitative trait loci for baseline white blood cell count, platelet count, and mean platelet volume. Mamm Genome 16:749–763

    Article  PubMed  Google Scholar 

  • Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, et al. (2006) The human obesity gene map: the 2005 update. Obesity 14:529–644

    PubMed  Google Scholar 

  • Seaton G, Haley CS, Knott SA, Kearsey M, Visscher PM (2002) QTL Express: mapping quantitative trait loci in simple and complex pedigrees. Bioinformatics 18:339–340

    Article  PubMed  CAS  Google Scholar 

  • Stoehr JP, Byers JE, Clee SM, Lan H, Boronenkov IV, et al. (2004) Identification of major quantitative trait loci controlling body weight variation in ob/ob mice. Diabetes 53:245–249

    Article  PubMed  CAS  Google Scholar 

  • Stylianou IM, Christians JK, Keightley PD, Bunger L, Clinton M, et al. (2004) Genetic complexity of an obesity QTL (Fob3) revealed by detailed genetic mapping. Mamm Genome 15:472–481

    Article  PubMed  CAS  Google Scholar 

  • Stylianou IM, Korstanje R, Li R, Sheehan S, Paigen B, et al. (2006) Quantitative trait locus analysis for obesity reveals multiple networks of interacting loci. Mamm Genome 17:22–36

    Article  PubMed  Google Scholar 

  • Wang S, Basten CJ, Zeng Z-B (2006). Windows QTL Cartographer 2.5. Department of Statistics, North Carolina State University, Raleigh, NC. Available at http://www.statgen.ncsu.edu/qtlcart/WQTLCart.htm/

  • Yi N, Zinniel DK, Kim K, Eisen EJ, Bartolucci A, et al. (2006) Bayesian analyses of multiple epistatic QTL models for body weight and body composition in mice. Genet Res 87:45–60

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank H. Kodama and T. Tanahashi for assistance with the animal care and genotyping. This work was supported by Grant-in-Aides for Scientific Research from the Japan Society for the Promotion of Science (Nos. 14560233 and 16380186) to A. Ishikawa.

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Authors and Affiliations

  1. Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, Aichi, 464-8601, Japan

    Akira Ishikawa, Eun-Hee Kim, Hasbaira Bolor, Md. Bazlur R. Mollah & Takao Namikawa

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  1. Akira Ishikawa
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  2. Eun-Hee Kim
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  3. Hasbaira Bolor
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  4. Md. Bazlur R. Mollah
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  5. Takao Namikawa
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Correspondence to Akira Ishikawa.

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Ishikawa, A., Kim, EH., Bolor, H. et al. A growth QTL (Pbwg1) region of mouse chromosome 2 contains closely linked loci affecting growth and body composition. Mamm Genome 18, 229–239 (2007). https://doi.org/10.1007/s00335-007-9009-5

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  • DOI: https://doi.org/10.1007/s00335-007-9009-5

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