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Identification of a congenic mouse line with obesity and body length phenotypes

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Abstract

Our primary objective was to discover simplified mouse models corresponding to human obesity linkages. We used the B10.UW– H3bwe Pax1unat/Sn (B10.UW) congenic strain, a subcongenic strain with a reduced UW strain donor region, and their C57BL/10SnJ background strain. The congenic and subcongenic UW strain donor regions are on mouse Chr 2. We measured body length [anal-nasal (AN) length], summed fat depot weights normalized for body weight (Adiposity Index, AI), and percentage of body weight that is lipid. The B10.UW congenic and subcongenic strains have significantly smaller AN lengths (p < 0.0001) and have a significantly lower AI and percentage of body weight as fat than the background strain (p < 0.0001). In an F2 intercross of the congenic and background strains, AN and AI were both linked to the distal half of the donor region with LOD scores greater than 19 and 5, respectively. F2 haplotypes identified a minimal region for AN linkage of 0.8 megabases (Mb) that is estimated to express four genes in the current Celera mouse genome assembly. We narrowed the most likely location of the obesity gene to 15 Mb whose homologous genes are all located on human Chr 20 in the region surrounding the centromere. Since a previous study identified human obesity linkage peaking near the centromere, then the B10.UW mice may exhibit obesity due to the homologous gene.

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References

  • TJ Aitman AM Glazier CA Wallace LD Cooper PJ Norsworthy et al. (1999) ArticleTitleIdentification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats Nat Genet 21 76–83 Occurrence Handle10.1038/5013 Occurrence Handle1:CAS:528:DyaK1MXltlWjsw%3D%3D Occurrence Handle9916795

    Article  CAS  PubMed  Google Scholar 

  • R Balling U Deutsch P Gruss (1988) ArticleTitleundulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1 Cell 55 531–535 Occurrence Handle10.1016/0092-8674(88)90039-6 Occurrence Handle1:CAS:528:DyaL1MXitVeq Occurrence Handle3180219

    Article  CAS  PubMed  Google Scholar 

  • R Balling C Ebensperger I Hoffmann K Imai H Koseki et al. (1993) ArticleTitleThe genetics of skeletal development Ann Genet 36 56–62 Occurrence Handle8503651 Occurrence Handle1:STN:280:DyaK3s3nslWgsg%3D%3D

    PubMed  CAS  Google Scholar 

  • GE Bell JS Stern (1977) ArticleTitleEvaluation of body composition of young obese and lean Zucker rats Growth 41 63–80 Occurrence Handle870396 Occurrence Handle1:STN:280:DyaE2s7mtlGhsg%3D%3D

    PubMed  CAS  Google Scholar 

  • JS Bodnar A Chatterjee LW Castellani DA Ross J Ohmen et al. (2002) ArticleTitlePositional cloning of the combined hyperlipidemia gene Hyplip1 Nat Genet 30 110–116 Occurrence Handle10.1038/ng811 Occurrence Handle1:CAS:528:DC%2BD38XivVGgsg%3D%3D Occurrence Handle11753387

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • MJ Brownstein JD Carpten JR Smith (1996) ArticleTitleModulation of non-templated nucleotide addition by Taq DNA polymerase: primer modifications that facilitate genotyping Biotechniques 20 1004–1006 Occurrence Handle8780871 Occurrence Handle1:CAS:528:DyaK28XjtlGmtr8%3D Occurrence Handle10.2144/96206st01

    Article  PubMed  CAS  Google Scholar 

  • YC Chagnon T Rankinen EE Snyder SJ Weisnagel L Perusse et al. (2003) ArticleTitleThe human obesity gene map: the 2002 update Obes Res 11 313–367 Occurrence Handle10.1038/oby.2003.47 Occurrence Handle1:CAS:528:DC%2BD3sXisVKgtLY%3D Occurrence Handle12634430

    Article  CAS  PubMed  Google Scholar 

  • JM Cheverud EJ Routman FA Duarte B Swinderen Particlevan K Cothran et al. (1996) ArticleTitleQuantitative trait loci for murine growth Genetics 142 1305–1319 Occurrence Handle8846907 Occurrence Handle1207127 Occurrence Handle1:CAS:528:DyaK28XivVGjur8%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  • PM Corva S Horvat JF Medrano (2001) ArticleTitleQuantitative trait loci affecting growth in high growth (hg) mice Mamm Genome 12 284–290 Occurrence Handle10.1007/s003350010275 Occurrence Handle1:CAS:528:DC%2BD3MXis12js7s%3D Occurrence Handle11309659

    Article  CAS  PubMed  Google Scholar 

  • AL Diament CH Warden (2004) ArticleTitleMultiple linked mouse chromosome 7 loci influence body fat mass Int J Obes Relat Metab Disord 28 199–210 Occurrence Handle10.1038/sj.ijo.0802516 Occurrence Handle1:CAS:528:DC%2BD2cXht12isLc%3D Occurrence Handle14569280

    Article  CAS  PubMed  Google Scholar 

  • C Dong S Wang WD Li D Li H Zhao et al. (2003) ArticleTitleInteracting genetic loci on chromosomes 20 and 10 influence extreme human obesity Am J Hum Genet 72 115–124 Occurrence Handle10.1086/345648 Occurrence Handle1:CAS:528:DC%2BD3sXis1ygtg%3D%3D Occurrence Handle12478478

    Article  CAS  PubMed  Google Scholar 

  • JA Floyd DA Gold D Concepcion TH Poon X Wang et al. (2003) ArticleTitleA natural allele of Nxf1 suppresses retrovirus insertional mutations Nat Genet 35 221–228 Occurrence Handle10.1038/ng1247 Occurrence Handle1:CAS:528:DC%2BD3sXosFWrsbc%3D Occurrence Handle14517553 Occurrence Handle2756099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • RJ Graff D Simmons J Meyer D Martin-Morgan M Kurtz (1986) ArticleTitleAbnormal bone production associated with mutant mouse genes pa and we J Hered 77 109–113 Occurrence Handle10.1093/oxfordjournals.jhered.a110179 Occurrence Handle1:STN:280:DyaL283isFelsA%3D%3D Occurrence Handle3711636

    Article  CAS  PubMed  Google Scholar 

  • CS Haley SA Knott (1992) ArticleTitleA simple regression method for mapping quantitative trait loci in line crosses using flanking markers Heredity 69 315–324 Occurrence Handle10.1038/hdy.1992.131 Occurrence Handle1:STN:280:DC%2BD283ovFaltQ%3D%3D Occurrence Handle16718932

    Article  CAS  PubMed  Google Scholar 

  • I Hirayama Z Yi S Izumi I Arai W Suzuki et al. (1999) ArticleTitleGenetic analysis of obese diabetes in the TSOD mouse Diabetes 48 1183–1191 Occurrence Handle10.2337/diabetes.48.5.1183 Occurrence Handle1:CAS:528:DyaK1MXjtFSgtL4%3D Occurrence Handle10331427

    Article  CAS  PubMed  Google Scholar 

  • SC Hunt V Abkevich CH Hensel A Gutin CD Neff et al. (2001) ArticleTitleLinkage of body mass index to chromosome 20 in Utah pedigrees Hum Genet 109 279–285 Occurrence Handle10.1007/s004390100581 Occurrence Handle1:CAS:528:DC%2BD3MXptVKqt74%3D Occurrence Handle11702208

    Article  CAS  PubMed  Google Scholar 

  • 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 Investig 100 1240–1247 Occurrence Handle10.1172/JCI119637 Occurrence Handle1:CAS:528:DyaK2sXlvFOgsbY%3D Occurrence Handle9276742

    Article  CAS  PubMed  Google Scholar 

  • RZ Ma J Gao ND Meeker PD Fillmore KS Tung et al. (2002) ArticleTitleIdentification of Bphs, an autoimmune disease locus, as histamine receptor H1 Science 297 620–623 Occurrence Handle10.1126/science.1072810 Occurrence Handle1:CAS:528:DC%2BD38XlslWrsL8%3D Occurrence Handle12142541

    Article  CAS  PubMed  Google Scholar 

  • 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 Investig 101 2485–2496 Occurrence Handle10.1172/JCI1748 Occurrence Handle1:CAS:528:DyaK1cXjvVajsbs%3D Occurrence Handle9616220

    Article  CAS  PubMed  Google Scholar 

  • DE Moody D Pomp MK Nielsen LD Vleck ParticleVan (1999) ArticleTitleIdentification of quantitative trait loci influencing traits related to energy balance in selection and inbred lines of mice Genetics 152 699–711 Occurrence Handle10353911 Occurrence Handle1460635 Occurrence Handle1:STN:280:DyaK1M3ot1Gjuw%3D%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  • TW Poole WK Silvers (1976) ArticleTitleThe development of regional pigmentation patterns in black and tan (at) mice J Exp Zool 197 115–119 Occurrence Handle10.1002/jez.1401970113 Occurrence Handle1:STN:280:DyaE283jvFKmug%3D%3D Occurrence Handle781177

    Article  CAS  PubMed  Google Scholar 

  • DR Reed X Li AH McDaniel K Lu S Li et al. (2003) ArticleTitleLoci 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 Occurrence Handle10.1007/s00335-002-2170-y Occurrence Handle1:CAS:528:DC%2BD3sXktlShsbw%3D Occurrence Handle12856282 Occurrence Handle1435867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • M Rhodes R Straw S Fernando A Evans T Lacey et al. (1998) ArticleTitleA high-resolution microsatellite map of the mouse genome Genome Res 8 531–542 Occurrence Handle10.1101/gr.8.5.531 Occurrence Handle1:CAS:528:DyaK1cXjt1arsbg%3D Occurrence Handle9582196

    Article  CAS  PubMed  Google Scholar 

  • EE Schadt SA Monks TA Drake AJ Lusis N Che et al. (2003) ArticleTitleGenetics of gene expression surveyed in maize, mouse and man Nature 422 297–302 Occurrence Handle10.1038/nature01434 Occurrence Handle1:CAS:528:DC%2BD3sXitFKmuro%3D Occurrence Handle12646919

    Article  CAS  PubMed  Google Scholar 

  • H Sone H Shimano Y Sakakura N Inoue M Amemiya-Kudo et al. (2002) ArticleTitleAcetyl-coenzyme A synthetase is a lipogenic enzyme controlled by SREBP-1 and energy status Am J Physiol Endocrinol Metab 282 E222–E230 Occurrence Handle10.1152/ajpendo.00189.2001 Occurrence Handle1:CAS:528:DC%2BD38XlsVKrtw%3D%3D Occurrence Handle11739104

    Article  CAS  PubMed  Google Scholar 

  • JP Stoehr JE Byers SM Clee H Lan IV Boronenkov et al. (2004) ArticleTitleIdentification of major quantitative trait loci controlling body weight variation in ob/ob mice Diabetes 53 245–249 Occurrence Handle10.2337/diabetes.53.1.245 Occurrence Handle1:CAS:528:DC%2BD2cXitlaltA%3D%3D Occurrence Handle14693723

    Article  CAS  PubMed  Google Scholar 

  • RT Stone JW Keele SD Shackelford SM Kappes M Koohmaraie (1999) ArticleTitleA primary screen of the bovine genome for quantitative trait loci affecting carcass and growth traits J Anim Sci 77 1379–1384 Occurrence Handle10.2527/1999.7761379x Occurrence Handle1:CAS:528:DyaK1MXjs1eqtrY%3D Occurrence Handle10375215

    Article  CAS  PubMed  Google Scholar 

  • MZ Strowski M Kohler HY Chen ME Trumbauer Z Li et al. (2003) ArticleTitleSomatostatin receptor subtype 5 regulates insulin secretion and glucose homeostasis Mol Endocrinol 17 93–106 Occurrence Handle10.1210/me.2001-0035 Occurrence Handle1:CAS:528:DC%2BD3sXmtFOhuw%3D%3D Occurrence Handle12511609

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • H Wang BR Gauthier KA Hagenfeldt-Johansson M Iezzi CB Wollheim (2002) ArticleTitleFoxa2 (HNF3beta) controls multiple genes implicated in metabolism-secretion coupling of glucose-induced insulin release J Biol Chem 277 17564–17570 Occurrence Handle10.1074/jbc.M111037200 Occurrence Handle1:CAS:528:DC%2BD38XktVCgtbk%3D Occurrence Handle11875061

    Article  CAS  PubMed  Google Scholar 

  • CH Warden JS Fisler SM Shoemaker PZ Wen KL Svenson et al. (1995) ArticleTitleIdentification of four chromosomal loci determining obesity in a multifactorial mouse model J Clin Investig 95 1545–1552 Occurrence Handle10.1172/JCI117827 Occurrence Handle1:CAS:528:DyaK2MXkslyktrw%3D Occurrence Handle7706460

    Article  CAS  PubMed  Google Scholar 

  • C Wolfrum DQ Shih S Kuwajima AW Norris CR Kahn et al. (2003) ArticleTitleRole of Foxa-2 in adipocyte metabolism and differentiation J Clin Investig 112 345–356 Occurrence Handle10.1172/JCI18698 Occurrence Handle1:CAS:528:DC%2BD3sXmtFemsbY%3D Occurrence Handle12865419

    Article  CAS  PubMed  Google Scholar 

  • B York AA Truett MP Monteiro SJ Barry CH Warden et al. (1999) ArticleTitleGene-environment interaction: a significant diet-dependent obesity locus demonstrated in a congenic segment on mouse chromosome 7 Mamm Genome 10 457–462 Occurrence Handle10.1007/s003359901023 Occurrence Handle1:CAS:528:DyaK1MXkt1Olsbc%3D Occurrence Handle10337618

    Article  CAS  PubMed  Google Scholar 

  • X Zhu A Zhou A Dey C Norrbom R Carroll et al. (2002) ArticleTitleDisruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects Proc Natl Acad Sci USA 99 10293–10298 Occurrence Handle10.1073/pnas.162352599 Occurrence Handle1:CAS:528:DC%2BD38Xmt1Citbo%3D Occurrence Handle12145326

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by National Institutes of Health grant R01 DK52581, NIH training grants PHS DK07355 and T32 GM007377, and the UC Davis Clinical Nutrition Research Unit, NIH DK35747. We thank Susan Bennett and Noreen Shibata for their excellent work managing the mouse colonies.

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Authors and Affiliations

  1. Rowe Program in Human Genetics, Section of Neurobiology/Physiology/Behavior, University of California, Davis, California, USA

    Craig H. Warden

  2. Myriad Genetics, Salt Lake City, Utah, USA

    Steven Stone, Donna Shattuck & Robyn Riley

  3. Department of Pediatrics, University of California, Davis, California, USA

    Craig H. Warden, Sally Chiu, Adam L. Diament & Juliet Easlick

  4. Department of Animal Science, University of Mar del Plata Balcarce, Argentina

    Pablo Corva

  5. Cardiovascular Genetics Research Program, University of Utah School of Medicine, Salt Lake City, Utah, USA

    Steven C. Hunt

  6. Department of Nutrition, University of California, Davis, California, USA

    Janis S. Fisler

  7. Department of Animal Science, University of California, Davis, USA

    Juan F. Medrano

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  1. Craig H. Warden
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  2. Steven Stone
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  3. Sally Chiu
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  4. Adam L. Diament
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Correspondence to Craig H. Warden.

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Warden, C.H., Stone, S., Chiu, S. et al. Identification of a congenic mouse line with obesity and body length phenotypes. Mamm Genome 15, 460–471 (2004). https://doi.org/10.1007/s00335-004-2353-9

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