Genetics of body weight in the LXS recombinant inbred mouse strains (original) (raw)

Abstract

This is the first phenotypic analysis of 75 new recombinant inbred (RI) strains derived from ILS and ISS progenitors. We analyzed body weight in two independent cohorts of female mice at various ages and in males at 60 days. Body weight is a complex trait which has been mapped in numerous crosses in rodents. The LXS RI strains displayed a large range of weights, transgressing those of the inbred progenitors, supporting the utility of this large panel for mapping traits not selected in the progenitors. Numerous QTLs for body weight mapped in single- and multilocus scans. We assessed replication between these and previously reported QTLs based on overlapping confidence intervals of published QTLs for body weight at 60 days and used meta-analyses to determine combined p values for three QTL regions located on Chromosomes 4, 5, and 11. Strain distribution patterns of microsatellite marker genotypes, weight, and other phenotypes are available on WebQTL (http://www.webqtl.org/search.html) and allow genetic mapping of any heritable quantitative phenotype measured in these strains. We report one such analysis, correlating brain and body weights. Large reference panels of RI strains, such as the LXS, are invaluable for identifying genetic correlations, GXE (Gene X Environment) interactions, and replicating previously identified QTLs.

Access this article

Log in via an institution

Subscribe and save

• Get 10 units per month
• Download Article/Chapter or eBook
• 1 Unit = 1 Article or 1 Chapter
• Cancel anytime Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

• Andersson L, Haley CS, Ellegren H, Knott S, Johansson M, et al. (1994) Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 263: 1771–1774
  PubMed Google Scholar
• Atchley WR, Zhu J (1997) Developmental quantitative genetics, conditional epigenetic variability and growth in mice. Genetics 147: 765–776
  PubMed Google Scholar
• Beavis WD (1994) The power and deceit of QTL experiments: Lessons from comparative QTL studies. 49th Annual Corn and Sorghum Research Conference, Johnston, IA. In: Proc. 49th Annual Corn and Sorgham Industry Research Conf., ASTA, Washington DC, 1994, 250–266
• Belknap JK (1998) Effect of within-strain sample size on QTL detection and mapping using recombinant inbred mouse strains. Behav Genet 28: 29–38
  Article PubMed Google Scholar
• Belknap JK, Mitchell SR, O’Toole LA, Helms ML, Crabbe JC (1996) Type I and type II error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains. Behav Genet 26: 149–160
  PubMed Google Scholar
• Bennett B, Beeson M, Gordon L, Johnson TE (2002) Reciprocal congenics defining individual quantitative trait loci for sedative/hypnotic sensitivity to ethanol. Alcohol Clin Exp Res 26: 149–157
  PubMed Google Scholar
• Brockmann GA, Bevova MR (2002) Using mouse models to dissect the genetics of obesity. Trends Genet 18: 367–376
  Article PubMed Google Scholar
• Brockmann GA, Haley CS, Renne U, Knott SA, Schwerin M (1998) Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth. Genetics 150: 369–381
  PubMed Google Scholar
• Brockmann GA, Kratzsch J, Haley CS, Renne U, Schwerin M, et al. (2000) Single QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F2 variance of growth and obesity in DU6i x DBA/2 mice. Genome Res 10: 1941–1957
  Article PubMed Google Scholar
• Broman KW, Wu H, Sen S, Churchill GA (2003) R/QTL: QTL mapping in experimental crosses. Bioinfomatics 19: 889–890
  Article Google Scholar
• Bünger L, Hill WG (1999) Inbred lines of mice derived from long-term divergent selection on fat content and body weight. Mamm Genome 10: 645–648
  Article PubMed Google Scholar
• Bünger L, Renne U, Buis RC (2001) Body weight limits in mice—long-term selection and single genes. In Encyclopedia of Genetics, ECG Reeve, ed. (London, Chicago: Fitzroy Dearborn Publishers), pp 337–360
  Google Scholar
• Chesler EJ (2002) Use of inbred strains for the study of individual differences in pain related phenotypes. Ph.D. dissertation, p. 20. Available at http://www.nervenet.org/main/dictionary.html
• Chesler EJ, Rodriguez-Zas SL, Mogil JS (2001) In silico mapping of mouse quantitative trait loci. Science 294: p 2423
  Article Google Scholar
• Chesler EJ, Wang JB, Lu L, Qu Y, Manly KF, et al. (2003) Genetic correlates of gene expression in recombinant inbred strains: A relational model system to explore neurobehavioral phenotypes. Neuroinformatics 1: 343–357
  Article PubMed Google Scholar
• Cheverud J, Routman E, Duarte FA, Van Swinderen B, Cothran K, et al. (1996) Quantitative trait loci for murine growth. Genetics 142: 1305–1319
  PubMed Google Scholar
• Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138: 963–971
  PubMed Google Scholar
• Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, et al. (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet 36: 1133–1137
  Article PubMed Google Scholar
• DeFries JC, Wilson JR, Erwin VG, Petersen DR (1989) LS x SS recombinant inbred strains of mice: Initial characterization. Alcohol Clin Exp Res 13: 196–200
  PubMed Google Scholar
• Falconer DS (1953) Selection for large and small size in mice. J Genet 51: 470–501
  Google Scholar
• Falconer DS, Mackay TF (1996) Introduction to Quantitative Genetics (Essex, England: Addison Wesley Longman Ltd.)
  Google Scholar
• Grupe A, Germer S, Usuka J, Aud D, Belknap JK (2001) In silico mapping of complex disease-related traits in mice. Science 292: 1915–1918
  Article PubMed Google Scholar
• Haley CS (1995) Livestock QTLs—bringing home the bacon? Trends Genet 11: 488–492
  Article PubMed Google Scholar
• Herbert JS, Kidwell JF, Chase HB (1979) The inheritance of growth and form in the mouse. IV. Changes in the variance components of weight, tail length and tail width during growth. Growth 43: 36–46
  PubMed Google Scholar
• Johnson TE, DeFries JC, Markel PD (1992) Mapping quantitative trait loci for behavioral traits in the mouse. Behav Genet 22: 635–653
  Article PubMed Google Scholar
• Keightley PD, Hardge T, May L, Bulfield G (1996) A genetic map of quantitative trait loci for body weight in the mouse. Genetics 142: 227–235
  PubMed Google Scholar
• Lander E, Kruglyak L (1995) Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results. Nat Genet 11: 241–247
  Article PubMed Google Scholar
• Lu L, Airey DC, Williams RW (2001) Complex trait analysis of the hippocampus: Mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice. J Neurosci 21: 3503–3514
  PubMed Google Scholar
• Lynch M, Walsh B (1998) Genetics and Analysis of Quantitative Traits (Sunderland, MA: Sinauer Associates)
  Google Scholar
• Manly KF, Cudmore RH (2001) Map manager QTX, cross-platform software for genetic mapping. Mamm Genome 12: 930–932
  Article PubMed Google Scholar
• Manly KF, Olson JM (1999) Overview of QTL mapping software and introduction to map manager QT. Mamm Genome 10: 327–334
  Article PubMed Google Scholar
• Markel PD, DeFries JC, Johnson TE (1995) Use of repeated measures in an analysis of ethanol-induced loss of righting reflex in inbred long-sleep and short-sleep mice. Alcohol Clin Exp Res 19: 299–304
  PubMed Google Scholar
• Markel PD, Bennett B, Beeson MA, Gordon L, Simpson VJ, et al. (1996) Strain distribution patterns for genetic markers in the LSxSS recombinant-inbred series. Mamm Genome 7: 408–412
  Article PubMed Google Scholar
• McClearn GE, Plomin R, Gora-Maslak G, Crabbe JC (1991) The gene chase in behavioral science. Psychol Sci 2: 222–229
  Google Scholar
• Motlusky HJ (1999) Analyzing Data with Graphpad Prism, 4th ed. (San Diego, CA: GraphPad Software, Inc.)
  Google Scholar
• Poiley SM (1972) Growth tables for 66 strains and stocks of laboratory animals. Lab Anim Sci 22: 759
  Google Scholar
• Rhees BK, Atchley WR (2000) Body weight and tail length divergence in mice selected for rate of development. J Exp Zool 288: 151–164
  Article PubMed Google Scholar
• Rocha JL, Eisen EJ, Van Vleck LD, Pomp D (2004) A large-sample QTL study in mice: I. Growth. Mamm Genome 15: 83–99
  Article PubMed Google Scholar
• Rothschild MF, Liu H-C, Tuggle CK, Yu T-P, Wang L (1995) Analysis of pig chromosome 7 genetic markers for growth and carcass performance traits. Anim Breed Genet 112: 341–348
  Google Scholar
• Sokal R, Rohlf F (2000) Biometry (New York: W.H. Freeman)
  Google Scholar
• Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Renhua L, et al. (2004) Sex-and lineage-specific inheritance of depression-like behavior in the rat. Mamm Genome 15: 648–662
  Article PubMed Google Scholar
• Vaughn TT, Pletscher LS, Peripato A, King-Ellison K, Adams E (1999) Mapping quantitative trait loci for murine growth: A closer look at genetic architecture. Genet Res 74: 313–322
  Article PubMed Google Scholar
• Wang J, Williams RW, Manly KF (2003) WebQTL: Web-based complex trait analysis. Neuroinformatics 1: 299–308
  Article PubMed Google Scholar
• Williams RW, Bennett B, Lu L, Gu J, DeFries JC, et al. (2004) Genetic structure of the L × S panel of recombinant inbred mouse strains: A powerful resource for complex trait analysis. Mamm Genome 15: 637–647
  Article PubMed Google Scholar

Download references

Acknowledgments

The authors thank J. Salazar and J. Wah for careful and reliable animal care and breeding. They also thank Nancy Phares-Zook for her research contributions and for her outstanding job managing our many diverse databases. Linda Lou Wessman, Justin Springett, and Jessica Hall spent many hours weighing mice. The authors also thank their colleagues at IBG and elsewhere who gave advice throughout the study and read the many versions of the manuscript; these include Brad Rikke and Shwu-Yar Tsai. The authors owe a large debt to Drs. Robert W. Williams and Lu Lu at the University of Tennessee Health Science Center, for genotyping all LXS strains. Most of all, thanks to Dr. John DeFries for the vision to initiate this RI panel.

This work was supported by funds from the University of Colorado and grants from the NIH (RO1 AA08940, AA11984, and KO1 AA00195). Genotyping costs were supported in part by P20-MH 62009 (a Human Brain Project to Dr. Robert W. Williams) and the INIA Genotyping Core (U24AA13513 to LL and RWW). WebQTL work was supported in part by U01 AA014425-01A1 (to LL).

Author information

Authors and Affiliations

1. Institute for Behavioral Genetics, 447, University of Colorado at Boulder, Boulder, Colorado, 80309-0447, USA
   Beth Bennett, Phyllis J. Carosone-Link & Thomas E. Johnson
2. Center of Genomics and Bioinformatics, Institute of Neuroscience, Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA
   Lu Lu & Elissa J. Chesler
3. Department of Integrative Physiology, 354, University of Colorado at Boulder, Boulder, Colorado, 80309-0447, USA
   Thomas E. Johnson

Authors

1. Beth Bennett
   You can also search for this author inPubMed Google Scholar
2. Phyllis J. Carosone-Link
   You can also search for this author inPubMed Google Scholar
3. Lu Lu
   You can also search for this author inPubMed Google Scholar
4. Elissa J. Chesler
   You can also search for this author inPubMed Google Scholar
5. Thomas E. Johnson
   You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toBeth Bennett.

Electronic Supplementary Material

Rights and permissions

About this article

Cite this article

Bennett, B., Carosone-Link, P.J., Lu, L. et al. Genetics of body weight in the LXS recombinant inbred mouse strains.Mamm Genome 16, 764–774 (2005). https://doi.org/10.1007/s00335-005-0002-6

Download citation

• Received: 21 January 2005
• Accepted: 21 June 2005
• Published: 29 October 2005
• Issue Date: October 2005
• DOI: https://doi.org/10.1007/s00335-005-0002-6

Keywords