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Loci on Chromosomes 2, 4, 9, and 16 for body weight, body length, and adiposity identified in a genome scan of an F2 intercross between the 129P3/J and C57BL/6ByJ mouse strains

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Abstract

Mice have proved to be a powerful model organism for understanding obesity in humans. Single gene mutants and genetically modified mice have been used to identify obesity genes, and the discovery of loci for polygenic forms of obesity in the mouse is an important next step. To pursue this goal, the inbred mouse strains 129P3/J (129) and C57BL/6ByJ (B6), which differ in body weight, body length, and adiposity, were used in an F2 cross to identify loci affecting these phenotypes. Linkages were determined in a two-phase process. In the first phase, 169 randomly selected F2 mice were genotyped for 134 markers that covered all autosomes and the X Chromosome (Chr). Significant linkages were found for body weight and body length on Chr 2. In addition, we detected several suggestive linkages on Chr 2 (adiposity), 9 (body weight, body length, and adiposity), and 16 (adiposity), as well as two suggestive sex-dependent linkages for body length on Chrs 4 and 9. In the second phase, 288 additional F2 mice were genotyped for markers near these regions of linkage. In the combined set of 457 F2 mice, six significant linkages were found: Chr 2 (Bwq5, body weight and Bdln3, body length), Chr 4 (Bdln6, body length, males only), Chr 9 (Bwq6, body weight and Adip5, adiposity), and Chr 16 (Adip9, adiposity), as well as several suggestive linkages (Adip2, adiposity on Chr 2; Bdln4 and Bdln5, body length on Chr 9). In addition, there was a suggestive linkage to body length in males on Chr 9 (Bdln4). For adiposity, there was evidence for epistatic interactions between loci on Chr 9 (Adip5) and 16 (Adip9). These results reinforce the concept that obesity is a complex trait. Genetic loci and their interactions, in conjunction with sex, age, and diet, determine body size and adiposity in mice.

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References

  1. AA Bachmanov DR Reed MG Tordoff RA Price GK Beauchamp (2001) ArticleTitleNutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice. Physiol Behav 72 603–613 Occurrence Handle10.1016/S0031-9384(01)00412-7 Occurrence Handle1:CAS:528:DC%2BD3MXit1SitLs%3D Occurrence Handle11282146

    Article  CAS  PubMed  Google Scholar 

  2. AA Bachmanov DR Reed X Li S Li GK Beauchamp et al. (2002) ArticleTitleVoluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ × 129P3/J F2 intercross. Genome Res 12 1257–1268 Occurrence Handle10.1101/gr.129702 Occurrence Handle1:CAS:528:DC%2BD38Xmtl2rurw%3D Occurrence Handle12176933

    Article  CAS  PubMed  Google Scholar 

  3. C Basten B Weir Z-B Zeng (2001) QTL Cartographer (1.15 ed). Department of Statistics, North Carolina State University Raleigh

    Google Scholar 

  4. GA Brockmann MR Bevova (2002) ArticleTitleUsing mouse models to dissect the genetics of obesity. Trends Genet 18 367–376 Occurrence Handle10.1016/S0168-9525(02)02703-8 Occurrence Handle1:CAS:528:DC%2BD38XlsVOlsrY%3D Occurrence Handle12127777

    Article  CAS  PubMed  Google Scholar 

  5. G Brockmann D Timtchenko P Das U Renne G Freyer et al. (1996) ArticleTitleDetection of QTL for body weight and body fat content in mice using genetic markers. J Anim Breed Genet 113 373–379

    Google Scholar 

  6. GA Brockmann CS Haley U Renne SA Knott M Schwerin (1998) ArticleTitleQuantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth. Genetics 150 369–381 Occurrence Handle1:CAS:528:DyaK1cXmtFKgsLc%3D Occurrence Handle9725853

    CAS  PubMed  Google Scholar 

  7. GA Brockmann J Kratzsch CS Haley U Renne M Schwerin et al. (2000) ArticleTitleSingle QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F(2) variance of growth and obesity in DU6i × DBA/2 mice. Genome Res 10 1941–1957 Occurrence Handle11116089

    PubMed  Google Scholar 

  8. JM Cheverud EJ Routman FAM Duarte B van Swinderen K Cothran et al. (1996) ArticleTitleQuantitative trait loci for murine growth. Genetics 142 1305–1319 Occurrence Handle1:CAS:528:DyaK28XivVGjur8%3D Occurrence Handle8846907

    CAS  PubMed  Google Scholar 

  9. AC Collins ICA Martin BW Kirkpatrick (1993) ArticleTitleGrowth quantitative trait loci (QTL) on mouse Chromosome 10 in a Quackenbush-Swiss X C57BL/6J backcross. Mamm Genome 4 454–458 Occurrence Handle1:CAS:528:DyaK2cXhtlSmurY%3D Occurrence Handle8374208

    CAS  PubMed  Google Scholar 

  10. PM Corva S Horvat JF Medrano (2001) ArticleTitleQuantitative trait loci affecting growth in high growth (hg) mice. Mamm Genome 12 284–290 Occurrence Handle1:CAS:528:DC%2BD3MXis12js7s%3D Occurrence Handle11309659

    CAS  PubMed  Google Scholar 

  11. W Dietrich H Katz SE Lincoln H-S Shin J Friedman et al. (1992) ArticleTitleA genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131 423–447 Occurrence Handle1:CAS:528:DyaK38XlvVGrt7g%3D Occurrence Handle1353738

    CAS  PubMed  Google Scholar 

  12. TA Dragani Z-B Zeng F Canzian M Gariboldi MT Ghilarducci et al. (1995) ArticleTitleMapping of body weight loci on mouse Chromosome X. Mamm Genome 6 778–781 Occurrence Handle1:CAS:528:DyaK28XktVWlug%3D%3D Occurrence Handle8597632

    CAS  PubMed  Google Scholar 

  13. TA Drake E Schadt K Hannani JM Kabo K Krass et al. (2001) ArticleTitleGenetic loci determining bone density in mice with diet-induced atherosclerosis. Physiol Genomics 5 205–215 Occurrence Handle1:CAS:528:DC%2BD3MXjs12quro%3D Occurrence Handle11328966

    CAS  PubMed  Google Scholar 

  14. D Falconer (1989) Introduction to Quantitative Genetics. (3rd ed) J Wiley & Sons New York

    Google Scholar 

  15. Festing MF, Simpson EM, Davisson MT, Mobraaten LE (Web site), Revised nomenclature for strain 129 mice. The Jackson Laboratory, http:www.informatics.jax.org/mgihome/nomen/strain129.shtml

  16. B Hogan F Costantini E Lacy (1986) Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor Laboratory Press Cold Spring Harbor, N.Y.

    Google Scholar 

  17. S Horvat L Bunger VM Falconer P Mackay A Law et al. (2000) ArticleTitleMapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm Genome 11 2–7 Occurrence Handle1:CAS:528:DC%2BD3cXos12iug%3D%3D Occurrence Handle10602985

    CAS  PubMed  Google Scholar 

  18. A Ishikawa Y Matsuda T Namikawa (2000) ArticleTitleDetection of quantitative trait loci for body weight at 10 weeks from Philippine wild mice. Mamm Genome 11 824–830 Occurrence Handle10.1007/s003350010145 Occurrence Handle1:CAS:528:DC%2BD3cXnsleitLk%3D Occurrence Handle11003694

    Article  CAS  PubMed  Google Scholar 

  19. PD Keightley T Hardge L May G Bulfield (1996) ArticleTitleA genetic map of quantitative trait loci for body weight in the mouse. Genetics 142 227–235 Occurrence Handle1:CAS:528:DyaK28Xht1Cqtrg%3D Occurrence Handle8770600

    CAS  PubMed  Google Scholar 

  20. PD Keightley KH Morris A Ishikawa VM Falconer F Oliver (1998) ArticleTitleTest of candidate gene-quantitative trait locus association applied to fatness in mice. Heredity 81 630–637 Occurrence Handle10.1038/sj.hdy.6884500 Occurrence Handle9885188

    Article  PubMed  Google Scholar 

  21. BW Kirkpatrick A Mengelt N Schulman IC Martin (1998) ArticleTitleIdentification of quantitative trait loci for prolificacy and growth in mice. Mamm Genome 9 97–102 Occurrence Handle1:CAS:528:DyaK1cXhtFKktrs%3D Occurrence Handle9457667

    CAS  PubMed  Google Scholar 

  22. RF Klein SR Mitchell TJ Phillips JK Belknap ES Orwoll (1998) ArticleTitleQuantitative trait loci affecting peak bone mineral density in mice. J Bone Miner Res 13 1648–1656 Occurrence Handle1:CAS:528:DyaK1cXntFKru78%3D Occurrence Handle9797472

    CAS  PubMed  Google Scholar 

  23. R Kluge K Giesen G Bahrenberg L Plum JR Ortlepp (2000) ArticleTitleQuantitative trait loci for obesity and insulin resistance (Nob1, Nob2) and their interaction with the leptin receptor allele (LeprA720T/T1044I) in New Zealand obese mice. Diabetologia 43 1565–1572 Occurrence Handle1:CAS:528:DC%2BD3cXotFCrt7w%3D Occurrence Handle11151768

    CAS  PubMed  Google Scholar 

  24. E Lander L Kruglyak (1995) ArticleTitleGenetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11 241–247 Occurrence Handle1:CAS:528:DyaK2MXptlSjs74%3D Occurrence Handle7581446

    CAS  PubMed  Google Scholar 

  25. E Lander P Green J Abrahamson A Barlow M Daley et al. (1987) ArticleTitleMAPMAKER: An interactive complex package for constructing primary linkage maps of experimental and natural populations. Genomics 1 174–181 Occurrence Handle1:CAS:528:DyaL1cXhsVCksrk%3D Occurrence Handle3692487

    CAS  PubMed  Google Scholar 

  26. JH Lee DR Reed W-D Li W Xu E-J Joo et al. (1999) ArticleTitleGenome scan for human obesity and linkage to markers in 20q13. Am J Hum Genet 64 196–209 Occurrence Handle1:CAS:528:DyaK1MXht1els7o%3D Occurrence Handle9915959

    CAS  PubMed  Google Scholar 

  27. AV Lembertas L Perusse YC Chagnon JS Fisler CH Warden et al. (1997) ArticleTitleIdentification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. J Clin Invest 100 1240–1247 Occurrence Handle1:CAS:528:DyaK2sXlvFOgsbY%3D Occurrence Handle9276742

    CAS  PubMed  Google Scholar 

  28. M Mehrabian PZ Wen J Fisler RC Davis AJ Lusis (1998) ArticleTitleGenetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model. J Clin Invest 101 2485–2496 Occurrence Handle1:CAS:528:DyaK1cXjvVajsbs%3D Occurrence Handle9616220

    CAS  PubMed  Google Scholar 

  29. DE Moody D Pomp MK Nielsen LD Van Vleck (1999) ArticleTitleIdentification of quantitative trait loci influencing traits related to energy balance in selection and inbred lines of mice. Genetics 152 699–711 Occurrence Handle1:STN:280:DyaK1M3ot1Gjuw%3D%3D Occurrence Handle10353911

    CAS  PubMed  Google Scholar 

  30. KH Morris A Ishikawa PD Keightley (1999) ArticleTitleQuantitative trait loci for growth traits in C57BL/6J × DBA/2J mice. Mamm Genome 10 225–228 Occurrence Handle1:CAS:528:DyaK1MXhs1OlsLw%3D Occurrence Handle10051315

    CAS  PubMed  Google Scholar 

  31. InstitutionalAuthorNameMouse Genome Sequencing Consortium (2002) ArticleTitleInitial sequencing and comparative analysis of the mouse genome. Nature 420 520–562 Occurrence Handle10.1038/nature01262 Occurrence Handle12466850

    Article  PubMed  Google Scholar 

  32. KA Rance SC Heath PD Keightley (1997a) ArticleTitleMapping quantitative trait loci for body weight on the X chromosome in mice. II. Analysis of congenic backcrosses. Genet Res 70 125–133 Occurrence Handle1:STN:280:DyaK1c7htVymsg%3D%3D

    CAS  Google Scholar 

  33. KA Rance WG Hill PD Keightley (1997b) ArticleTitleMapping quantitative trait loci for body weight on the X chromosome in mice. I. Analysis of a reciprocal F2 population. Genet Res 70 117–124 Occurrence Handle1:STN:280:DyaK1c7htVynuw%3D%3D

    CAS  Google Scholar 

  34. PC Reifsnyder G Churchill EH Leiter (2000) ArticleTitleMaternal environment and genotype interact to establish diabesity in mice. Genome Res 10 1568–1578 Occurrence Handle10.1101/gr.147000 Occurrence Handle1:CAS:528:DC%2BD3cXns1Siu7Y%3D Occurrence Handle11042154

    Article  CAS  PubMed  Google Scholar 

  35. TH Roderick JN Guidi (1989) Strain distribution of polymorphic variants. MF Lyon AG Searle (Eds) Genetic Variants and Strains of the Laboratory Mouse (2nd ed). Oxford University Press New York 663–672

    Google Scholar 

  36. WK Silvers (1979) The Coat Colors of Mice, a Model for Mammalian Gene Action and Interaction. Springer-Verlag New York

    Google Scholar 

  37. BA Taylor SJ Phillips (1996) ArticleTitleDetection of obesity QTLs on mouse chromosomes 1 and 7 by selective DNA pooling. Genomics 34 389–398 Occurrence Handle10.1006/geno.1996.0302 Occurrence Handle1:CAS:528:DyaK28XktV2htrc%3D Occurrence Handle8786140

    Article  CAS  PubMed  Google Scholar 

  38. BA Taylor SJ Phillips (1997) ArticleTitleObesity QTLs on mouse chromosomes 2 and 17. Genomics 43 249–257 Occurrence Handle10.1006/geno.1997.4835 Occurrence Handle1:CAS:528:DyaK2sXlsFeisLw%3D Occurrence Handle9268627

    Article  CAS  PubMed  Google Scholar 

  39. BA Taylor LM Tarantino SJ Phillips (1999) ArticleTitleGender-influenced obesity QTLs identified in a cross involving the KK type II diabetes-prone mouse strain. Mamm Genome 10 963–968 Occurrence Handle10.1007/s003359901141 Occurrence Handle1:CAS:528:DyaK1MXmtlCru7o%3D Occurrence Handle10501964

    Article  CAS  PubMed  Google Scholar 

  40. BA Taylor C Wnek D Schroeder SJ Phillips (2001) ArticleTitleMultiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains. Mamm Genome 12 95–103 Occurrence Handle10.1007/s003350010254 Occurrence Handle1:CAS:528:DC%2BD3MXhsFSgtr8%3D Occurrence Handle11210195

    Article  CAS  PubMed  Google Scholar 

  41. GE Truett P Heeger RL Mynatt AA Truett JA Walker et al. (2000) ArticleTitlePreparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris (HotSHOT). Biotechniques 29 52–54 Occurrence Handle1:CAS:528:DC%2BD3cXkslOlsL0%3D Occurrence Handle10907076

    CAS  PubMed  Google Scholar 

  42. CM Wade EJ Kulbokas AW Kirby MC Zody JC Mullikin et al. (2002) ArticleTitleThe mosaic structure of variation in the laboratory mouse genome. Nature 420 574–578 Occurrence Handle10.1038/nature01252 Occurrence Handle1:CAS:528:DC%2BD38Xpt1WhsL4%3D Occurrence Handle12466852

    Article  CAS  PubMed  Google Scholar 

  43. CH Warden JS Fisler MJ Pace KL Svenson AJ Lusis (1993) ArticleTitleCoincidence of genetic loci for plasma cholesterol levels and obesity in a multifactorial mouse model. J Clin Invest 92 773–779 Occurrence Handle1:CAS:528:DyaK2cXkslWjug%3D%3D Occurrence Handle8349816

    CAS  PubMed  Google Scholar 

  44. CH Warden JS Fisler SM Shoemaker P-Z Wen KL Svenson (1995) ArticleTitleIdentification of four chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest 95 1545–1552 Occurrence Handle1:CAS:528:DyaK2MXkslyktrw%3D Occurrence Handle7706460

    CAS  PubMed  Google Scholar 

  45. DB West J Goudey-Lefevre B York GE Truett (1994a) ArticleTitleDietary obesity linked to genetic loci on chromosome 9 and 15 in a polygenic mouse rnodel. J Clin Invest 94 1410–1416 Occurrence Handle1:CAS:528:DyaK2cXmvFCiu70%3D

    CAS  Google Scholar 

  46. DB West J Waguespack B York J Goudey-Lefevre RA Price (1994b) ArticleTitleGenetics of dietary obesity in AKR/J × SWR/J mice: segregation of the trait and identification of a linked locus on Chromosome 4. Mamm Genome 5 546–552 Occurrence Handle1:CAS:528:DyaK2MXhtlyjt74%3D

    CAS  Google Scholar 

  47. DB West GE Truett J Goudey-Lefevre B York (1995) ArticleTitleLoci on chromosomes 4, 7, 9, 12 & 15 control a significant proportion of the dietary obesity phenotype in the mouse. FASEB 9 A722

    Google Scholar 

  48. Withham B (1990) Coat colors of sublines of 129 mice. JAX notes, no. 441

  49. B York K Lei DB West (1996) ArticleTitleSensitivity to dietary obesity linked to a locus on Chromosome 15 in a CAST/Ei × C57BL/6J F2 intercross. Mamm Genome 7 677–681 Occurrence Handle10.1007/s003359900204 Occurrence Handle1:CAS:528:DyaK28XmvFOjurc%3D Occurrence Handle8703121

    Article  CAS  PubMed  Google Scholar 

  50. B York K Lei DB West (1997) ArticleTitleInherited non-autosomal effects on body fat in F2 mice derived from an AKR/J × SWR/J cross. Mamm Genome 8 726–730 Occurrence Handle10.1007/s003359900554 Occurrence Handle1:CAS:528:DyaK2sXmsleisb0%3D Occurrence Handle9321464

    Article  CAS  PubMed  Google Scholar 

  51. Z-B Zeng (1993) ArticleTitleTheoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc Natl Acad Sci USA 90 10972–10976 Occurrence Handle1:CAS:528:DyaK2cXkslWlsQ%3D%3D Occurrence Handle8248199

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Institutes of Health grants R01DC00882 (Gary K Beauchamp); R03DC03509, R01DC04188, and R01DK55853 (D.R.Reed); R01AA11028 (M.G.Tordoff); and R03DC03853 (A.A.Bachmanov). We gratefully acknowledge the technical assistance of Maria Theodorides.

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Authors and Affiliations

  1. Monell Chemical Senses Center, 3500 Market Street, Philadelphia, Pennsylvania 19104, USA

    Danielle R. Reed, Xia Li, Amanda H. McDaniel, Ke Lu, Shanru Li, Michael G. Tordoff & Alexander A. Bachmanov

  2. University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

    Arlen R. Price

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  1. Danielle R. Reed
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  2. Xia Li
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  3. Amanda H. McDaniel
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Correspondence to Danielle R. Reed.

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Reed, D.R., Li, X., McDaniel, A.H. et al. Loci on Chromosomes 2, 4, 9, and 16 for body weight, body length, and adiposity identified in a genome scan of an F2 intercross between the 129P3/J and C57BL/6ByJ mouse strains . Mamm Genome 14, 302–313 (2003). https://doi.org/10.1007/s00335-002-2170-y

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