Abstract
In an intercross between the high-body-weight-selected mouse line NMRI8 and the inbred line DBA/2, we analyzed genetic effects on growth during the suckling period and after weaning during the juvenile phase of development. QTL mapping results indicated that a switch of gene activation might occur at the age of three weeks when animals are weaned. We found QTLs for body weight with major effects at the age of two and three weeks when animals are fed by their mothers, and QTLs with highest effects after weaning when animals have to live on their own under ad libitum access to food. Specific epistatic effects on body weight at two and three weeks and epistatic interaction influencing growth after weaning support this finding. QTL effects explained the greatest variance during puberty when animals grow fastest and become fertile. In the present study, all except one QTL effect for early body weight had dominance variance components. These might result from direct single-locus-dominant allelic expression, but also from the identified epistatic interaction between different QTLs that we have found for body weight at all ages. Beside body weight, body composition traits (muscle weight, reproductive fat weight, weight of inner organs) were analyzed. Sex-dimorphic QTLs were found for body weight and fat deposition. The identified early-growth QTLs could be the target of epigenetic modifications which might influence body weight at later ages.
Similar content being viewed by others
References
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
GA Brockmann C Haley U Renne SA Knott M Schwerin (1998) ArticleTitleQTLs affecting body weight and fatness from a mouse line selected for high growth Genetics 150 369–381 Occurrence Handle1:CAS:528:DyaK1cXmtFKgsLc%3D Occurrence Handle9725853
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 F2 variance of growth and obesity in DU6i × DBA/2 mice Genome Res 10 1941–1957 Occurrence Handle10.1101/gr.GR1499R Occurrence Handle1:CAS:528:DC%2BD3MXjs1Y%3D Occurrence Handle11116089
GA Brockmann CS Haley E Wolf S Karle J Kratzsch et al. (2001) ArticleTitleGenome-wide search for loci controlling serum IGF binding protein levels of mice FASEB J 15 978–987 Occurrence Handle10.1096/fj.00-0391com Occurrence Handle1:CAS:528:DC%2BD3MXivFOrtL0%3D Occurrence Handle11292658
L Bunger A Laidlaw G Bulfield EJ Eisen JF Medrano et al. (2001) ArticleTitleInbred lines of mice derived from long-term growth selected lines: unique resources for mapping growth genes Mamm Genome 12 678–686 Occurrence Handle10.1007/s00335-001-3018-6 Occurrence Handle1:CAS:528:DC%2BD3MXnt1CqtL4%3D Occurrence Handle11641715
I Butler F Pirchner (1983) ArticleTitleEffectiveness of within family and individual selection for increased 3 to 5 weeks body weight gain in different mouse populations Züchtungskunde 55 241–246
O Carlborg S Kerje K Schutz L Jacobsson P Jensen et al. (2003) ArticleTitleA global search reveals epistatic interaction between QTL for early growth in the chicken Genome Res 13 413–421 Occurrence Handle10.1101/gr.528003 Occurrence Handle1:CAS:528:DC%2BD3sXit1Wgt70%3D Occurrence Handle12618372
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 Handle1:CAS:528:DC%2BD3sXisVKgtLY%3D Occurrence Handle12634430
JM Cheverud EJ Routman (1995) ArticleTitleEpistasis and its contribution to genetic variance components Genetics 139 1455–1461 Occurrence Handle1:STN:280:ByqB1cngslU%3D Occurrence Handle7768453
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 Handle1:CAS:528:DyaK28XivVGjur8%3D Occurrence Handle8846907
JM Cheverud TT Vaughn LS Pletscher AC Peripato ES Adams et al. (2001) ArticleTitleGenetic architecture of adiposity in the cross of LG/J and SM/J inbred mice Mamm Genome 12 3–12 Occurrence Handle10.1007/s003350010218 Occurrence Handle1:CAS:528:DC%2BD3MXptlGqsw%3D%3D Occurrence Handle11178736
GA Churchill RW Doerge (1994) ArticleTitleEmpirical threshold values for quantitative trait mapping Genetics 138 963–971 Occurrence Handle1:STN:280:ByqC2MvntFw%3D Occurrence Handle7851788
M Dhar LS Webb L Smith L Hauser D Johnson et al. (2000) ArticleTitleA novel ATPase on mouse Chr 7 is a candidate gene for increased body fat Physiol Genomics 4 93–100 Occurrence Handle1:CAS:528:DC%2BD3cXoslektbs%3D Occurrence Handle11074018
WF Dietrich J Miller R Steen MA Merchant D Damron–Boles et al. (1996) ArticleTitleA comprehensive genetic map of the mouse genome Nature 380 149–152 Occurrence Handle10.1038/380149a0 Occurrence Handle1:CAS:528:DyaK28Xhs1Gns7Y%3D Occurrence Handle8600386
CS Haley SA Knott LM Elsen (1994) ArticleTitleMapping quantitative trait loci in crosses between outbred lines using least squares Genetics 136 1195–1207 Occurrence Handle1:CAS:528:DyaK2MXpsFCr Occurrence Handle8005424
LD Hurst EJ Williams C Pal (2002) ArticleTitleNatural selection promotes the conservation of linkage of co-expressed genes Trends Genet 18 604–606 Occurrence Handle10.1016/S0168-9525(02)02813-5 Occurrence Handle1:CAS:528:DC%2BD38XoslCgtbc%3D Occurrence Handle12446137
R Jaenisch A Bird (2003) ArticleTitleEpigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals Nat Genet 33 Suppl 245–254 Occurrence Handle10.1038/ng1089
RC Jansen (1993) ArticleTitleInterval mapping of multiple quantitative trait loci Genetics 135 205–211 Occurrence Handle1:CAS:528:DyaK2cXpslensg%3D%3D Occurrence Handle8224820
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
SA Knott L Marklund CS Haley K Andersson W Davies et al. (1998) ArticleTitleMultiple marker mapping of quantitative trait loci in an outbred cross between wild boar and Large White pigs Genetics 149 1069–1080 Occurrence Handle1:CAS:528:DyaK1cXks1eht70%3D Occurrence Handle9611214
E Lander P Green (1987) ArticleTitleConstruction of multilocus genetic linkage maps in humans Proc Nat Acad Sci USA 84 2363–2367 Occurrence Handle1:STN:280:BiiC2srmslc%3D Occurrence Handle3470801
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
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 Handle1:STN:280:DyaK1M3ot1Gjuw%3D%3D Occurrence Handle10353911
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 Handle10.1007/s003359900977 Occurrence Handle1:CAS:528:DyaK1MXhs1OlsLw%3D Occurrence Handle10051315
SW Omholt E Plahte L Oyehaug K Xiang (2000) ArticleTitleGene regulatory networks generating the phenomena of additivity, dominance and epistasis Genetics 155 969–980 Occurrence Handle1:STN:280:DC%2BD3cvislKrug%3D%3D Occurrence Handle10835414
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
InstitutionalAuthorNameInstitute SAS (1989) SAS/STAT User’s Guide, Version 6, 4th ed SAS Institute Inc. Cary, NC
TT Vaughn LS Pletscher A Peripato K King–Ellison E Adams et al. (1999) ArticleTitleMapping quantitative trait loci for murine growth—a closer look at genetic architecture Genet Res 74 313–322 Occurrence Handle10.1017/S0016672399004103 Occurrence Handle1:CAS:528:DC%2BD3cXhs1Grtbc%3D Occurrence Handle10689807
CM Wade EJ Kulbokas Suffix3rd 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
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
Acknowledgments
The German Research Foundation, Grant No. BR 1285/4, and the H. Wilhelm Schaumann Stiftung supported this work. C.S.H. acknowledges support from the BBSRC (Biotechnology and Biological Sciences Research Council). Excellent technical assistance was provided by Hannelore Tychsen for DNA preparation and genotyping.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Brockmann, G.A., Karatayli, E., Haley, C.S. et al. QTLs for pre- and postweaning body weight and body composition in selected mice. Mamm Genome 15, 593–609 (2004). https://doi.org/10.1007/s00335-004-3026-4
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00335-004-3026-4