Journal of Genetics

, Volume 97, Issue 5, pp 1413–1420 | Cite as

Quantitative trait loci that determine plasma insulin levels in \(\hbox {F}_{2}\) intercross populations produced from crosses between DDD/Sgn and C57BL/6J inbred mice

  • Jun-Ichi SutoEmail author
  • Misaki Kojima
Research Article


When compared to C57BL/6J (B6) mice, DDD/Sgn (DDD) mice has substantially higher plasma insulin levels in both sexes. In this study, we performed quantitative trait loci (QTL) mapping of plasma insulin levels in \(\hbox {F}_{2}\) male mice produced by crosses between DDD and B6 mice. By single-QTL scans, we identified one significant QTL on chromosome 9. When body weight was included as an additive covariate, we identified two significant QTL on chromosomes 9 and 12; the latter coincided with a QTL that was previously identified in \(\hbox {F}_{2}\) female mice produced by the same two strains. The inheritance mode and the direction of the allelic effect of QTL on chromosome 12 were similar in both sexes, but those on chromosome 9 differed between males and females, suggesting that the QTL on chromosome 9 was sex-specific. Based on phenotypic correlations of plasma insulin levels with body weight and plasma levels of total cholesterol, triglyceride and testosterone, we subsequently assessed whether these insulin QTL explain the variation in other metabolic traits by using a point-wise significance threshold of \(P = 0.05\). QTL on chromosome 12 had no significant effect on any trait. In contrast, QTL on chromosome 9 had significant effects on body weight and total cholesterol level. We postulate that Gpr68 and Cyp19a1 are plausible candidate genes for QTL on chromosomes 12 and 9, respectively. These findings provide insight into the genetic mechanisms underlying insulin metabolism.


DDD/Sgn mice plasma insulin level quantitative trait loci mapping 



This study was supported in part by the NIAS (National Institute of Agrobiological Sciences) Strategic Research Fund.


  1. Broman K. W. and Sen Ś. 2009 A guide to QTL mapping with R/qtl. Springer, New York.CrossRefGoogle Scholar
  2. Broman K. W., Wu H., Sen Ś. and Churchill G. A. 2003 R/qtl: QTL mapping in experimental crosses. Bioinformatics 19, 889–890.CrossRefGoogle Scholar
  3. Churchill G. A. and Doerge R. W. 1994 Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.PubMedPubMedCentralGoogle Scholar
  4. Kido Y., Philippe N., Schäffer A. A. and Accili D. 2000 Genetic modifiers of the insulin resistance phenotype in mice. Diabetes 49, 589–596.CrossRefGoogle Scholar
  5. Lander E. and Kruglyak L. 1995 Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat. Genet. 11, 241–247.CrossRefGoogle Scholar
  6. Purcell-Huynh D. A., Weinreb A., Castellani L. W., Mehrabian M., Doolittle M. H. and Lusis A. J. 1995 Genetic factors in lipoprotein metabolism. Analysis of a genetic cross between inbred mouse strains NZB/B1NJ and SM/J using a complete linkage map approach. J. Clin. Invest. 96, 1845–1858.CrossRefGoogle Scholar
  7. Schmidt C., Gonzaludo N. P., Strunk S., Dahm S., Schuchhardt J., Kleinjung F. et al. 2008 A meta-analysis of QTL for diabetes-related traits in rodents. Physiol. Genomics 34, 42–53.CrossRefGoogle Scholar
  8. Sen Ś. and Churchill G. A. 2001 A statistical framework for quantitative trait mapping. Genetics 159, 371–387.PubMedPubMedCentralGoogle Scholar
  9. Suto J. 2013 QTL mapping of genes controlling plasma insulin and leptin concentrations: metabolic effect of obesity QTLs identified in an \(\text{ F }_{2}\) intercross between C57BL/6J and DDD.Cg-\(A^{y}\) inbred mice. J. Vet. Med. Sci. 75, 895–907.CrossRefGoogle Scholar
  10. Suto J. and Satou K. 2013 Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the \(A^{y}\) allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss. BMC Genet. 14, 35.CrossRefGoogle Scholar
  11. Suto J. and Satou K. 2015 Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-\(A^{y}\). J. Vet. Med. Sci. 77, 203–210.CrossRefGoogle Scholar
  12. Suto J. and Kojima M. 2017a Quantitative trait loci that control body weight in DDD/Sgn and C57BL/6J inbred mice. Mamm. Genome 28, 13–19.CrossRefGoogle Scholar
  13. Suto J. and Kojima M. 2017b Identification of quantitative trait loci that determine plasma total-cholesterol and triglyceride concentrations in DDD/Sgn and C57BL/6J inbred mice. Cholesterol. Article ID 3178204.Google Scholar
  14. Toye A. A., Lippiat J. D., Proks P., Shimomura K., Bentley L., Hugill A. et al. 2005 A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 48, 675–686.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Institute of Agrobiological SciencesNational Agriculture and Food Research Organization (NARO)TsukubaJapan
  2. 2.Institute of Livestock and Grassland ScienceNational Agriculture and Food Research Organization (NARO)TsukubaJapan

Personalised recommendations