Confirmation of Diabetes-Related Quantitative Trait Loci Derived from SM/J and A/J Mice by Using Congenic Strains Fed a High-Carbohydrate or High-Fat Diet

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  • KOBAYASHI Misato
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University
  • HADA Natsuko
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University
  • HOSHINO Hiromi
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University
  • OZAWA Takashi
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University
  • UMESHITA Kazuhiko
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University
  • NISHIMURA Masahiko
    Division of Experimental Animals, Center for Promotion of Medical Research and Education, Graduate School of Medicine, Nagoya University
  • MURAI Atsushi
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University
  • OHNO Tamio
    Division of Experimental Animals, Center for Promotion of Medical Research and Education, Graduate School of Medicine, Nagoya University
  • HORIO Fumihiko
    Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University

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Abstract

The interaction between causative genes and diet is known to influence the onset of obesity and diabetes in humans, although it has remained difficult to identify diabetogenic gene(s) because humans are genetically and environmentally heterogeneous. Mouse SMXA recombinant inbred (RI) strains are established from parental inbred strains (SM/J and A/J) and have been shown to be beneficial tools for analyzing polygenic traits. We previously mapped a significant quantitative trait locus (QTL, T2dm1sa) on Chromosome (Chr.) 10 and suggestive QTLs on Chr. 2, 6, and 18 for diabetes-related traits by using SMXA RI strains fed a high-carbohydrate diet. As a first step in identifying the responsible gene among QTLs for glucose tolerance mapped on Chr. 10 and 18, we established new strains of A.SM-T2dm1sa and SM.A-D18Mit19-D18Mit7 congenic mice. Each congenic strain bears the diabetogenic allele of an introgressed chromosomal region on a genetic background strain carrying the non-diabetogenic allele. The diabetogenic effect of T2dm1sa mapped on Chr. 10 was not supported by studies of A.SM-T2dm1sa congenic mice when the mice were fed a high-carbohydrate or high-fat diet. SM.A-D18Mit19-D18Mit7 congenic mice showed impaired glucose tolerance not only when they were fed a high-carbohydrate diet, but also when they were fed a high-fat diet. Thus, it appears that gene(s) affecting diabetes-related traits under either dietary condition may be present on Chr. 18.

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