International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

G.4 Characterization of Glucose Tolerance Quantitative Trait Loci on Mouse Chromosomes 11 and 14 Using Chromosome Substitution Strain

Naru Babaya1, Hiroshi Ikegami1, Yoshihiko Kawaguchi1, Tomomi Fujisawa1, Hironori Ueda1, Koji Nojima1, Michiko Itoi1, Kazunori Yamada1, Masao Shibata2 and Toshio Ogihara1.
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;
Aichi-Gakuin University, Aichi, Japan

Type 2 diabetes is a major public health problem in developed countries. Nevertheless, the genetic basis of type 2 diabetes remains poorly understood, mainly because of the heterogeneous nature of the disease.

The NSY mouse is an inbred strain which spontaneously develops type 2 diabetes and shows moderate obesity. In our previous study of a whole genome scan using (C3H x NSY)F2 mice, three major quantitative trait loci (QTLs) for glucose intolerance were detected and NSY-derived alleles on chromosomes 11, 14, 6 were shown to increase blood glucose levels (Nidd1n, Nidd2n, Nidd3n, respectively).

In the present study, for fine mapping and for future identification of the responsible gene at each locus, we adopted a marker-assisted method and created two autosomal chromosome substitution strains (CCSs), C3H.NSY-Chr11 and C3H.NSY-Chr14. At the age of 48 weeks, heterozygous C3H.NSY-Chr11, C3H.NSY-Chr14 and control C3H were analyzed. Overnight-fasted mice received intraperitoneal glucose challenge, and blood glucose levels were measured at 0, 30, 60, 90, 120 min.

C3H.NSY-Chr11 mice showed significantly higher blood glucose levels at fasting and all the time points after a glucose challenge than C3H mice. C3H.NSY-Chr14 mice exhibited significantly higher blood glucose levels after a glucose challenge than C3H mice, whereas they showed similar fasting glucose level to C3H mice. Body weight showed no significant difference among the three lines.

In conclusion, the higher glucose levels, despite similar body weight, observed in both CCSs than control mice demonstrated that Nidd1n and Nidd2n on chromosomes 11 and 14 affect glucose tolerance, but that their effects are independent of increased body weight.

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