Diabetic modifier QTL, Dbm4, affecting elevated fasting blood glucose concentrations in congenic mice

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Author(s)

Abstract

We have previously identified four significant quantitative trait loci (QTL) affecting plasma glucose concentrations on F<sub>2</sub> progeny of hypoinsulinemic diabetic Akita mice, heterozygous for the <i>Ins2</i> gene Cys96Tyr mutation, and non-diabetic A/J mice, one of which on chromosome 15 named <i>Dbm4</i> (<u>d</u>ia<u>b</u>etic <u>m</u>odifier QTL 4) was shown to affect fasting plasma glucose concentrations with a maximum LOD score of 6.17. To estimate the influence of <i>Dbm4</i> itself to the diabetes-related phenotypes, we constructed congenic strain with heterozygous <i>Ins2</i> mutation using the Akita allele as donor of <i>Dbm4</i> locus in the A/J genetic background, and measured quantitative traits including plasma glucose concentrations in glucose tolerance test (GTT). In this study, we found the Akita allele in <i>Dbm4</i> was associated with higher fasting plasma glucose concentrations as in previous QTL analysis. According to gene expression assay, key enzymes of hepatic gluconeogenesis were expressed to the more increased degree in the liver of congenic mice compared to the A/J allele based control mice. Based on these results, we concluded that diabetic modifier gene(s) exist on <i>Dbm4</i> locus affecting fasting plasma glucose concentrations via regulation of gluconeogenic gene expression in the hypoinsulinemic diabetic condition. Identification of the modifier gene responsible for <i>Dbm4</i> would provide new drug development targets for human type 2 diabetes with hepatic insulin resistance.

Journal

  • Genes & Genetic Systems

    Genes & Genetic Systems 87(5), 341-346, 2012-10-25

    The Genetics Society of Japan

References:  19

Codes

  • NII Article ID (NAID)
    10031155698
  • NII NACSIS-CAT ID (NCID)
    AA11077421
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    13417568
  • NDL Article ID
    024252525
  • NDL Call No.
    Z53-W539
  • Data Source
    CJP  NDL  J-STAGE 
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