Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11

The quantitative trait locus (QTL) mapping in segregating crosses of NSY (Nagoya-Shibata-Yasuda) mice, an animal model of type 2 diabetes, with nondiabetic strain C3H/He mice has identified diabetogenic QTLs on multiple chromosomes. The QTL on chromosome 11 (Chr11) (Nidd1n) showing the largest effec...

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Main Authors: Naru Babaya, Hironori Ueda, Shinsuke Noso, Yoshihisa Hiromine, Koji Nojima, Michiko Itoi-Babaya, Misato Kobayashi, Tomomi Fujisawa, Hiroshi Ikegami
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2013/608923
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author Naru Babaya
Hironori Ueda
Shinsuke Noso
Yoshihisa Hiromine
Koji Nojima
Michiko Itoi-Babaya
Misato Kobayashi
Tomomi Fujisawa
Hiroshi Ikegami
author_facet Naru Babaya
Hironori Ueda
Shinsuke Noso
Yoshihisa Hiromine
Koji Nojima
Michiko Itoi-Babaya
Misato Kobayashi
Tomomi Fujisawa
Hiroshi Ikegami
author_sort Naru Babaya
collection DOAJ
description The quantitative trait locus (QTL) mapping in segregating crosses of NSY (Nagoya-Shibata-Yasuda) mice, an animal model of type 2 diabetes, with nondiabetic strain C3H/He mice has identified diabetogenic QTLs on multiple chromosomes. The QTL on chromosome 11 (Chr11) (Nidd1n) showing the largest effect on hyperglycemia was confirmed by our previous studies with homozygous consomic mice, C3H-11NSY, in which the NSY-derived whole Chr11 was introgressed onto control C3H background genes. C3H-11NSY mice also showed a streptozotocin (STZ) sensitivity. In the present study, we constructed heterozygous C3H-11NSY mice and the phenotypes were analyzed in detail in comparison with those of homozygous C3H-11NSY and C3H mice. Heterozygous C3H-11NSY mice had significantly higher blood glucose levels and STZ sensitivity than those in C3H mice. Hyperglycemia and STZ sensitivity in heterozygous C3H-11NSY mice, however, were not as severe as in homozygous C3H-11NSY mice. The body weight and fat pad weight in heterozygous C3H-11NSY mice were similar to those in C3H and homozygous C3H-11NSY mice. These data indicated that the introgression of Chr11 of the diabetes-susceptible NSY strain onto diabetes-resistant C3H caused marked changes in the glucose tolerance and STZ susceptibility even in a heterozygous state, and suggested that the mode of inheritance of a gene or genes on Chr11 for hyperglycemia and STZ sensitivity is additive.
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spelling doaj-art-4c94f3c6980545dfa7b7bb3b507e8bc42025-08-20T02:38:36ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/608923608923Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11Naru Babaya0Hironori Ueda1Shinsuke Noso2Yoshihisa Hiromine3Koji Nojima4Michiko Itoi-Babaya5Misato Kobayashi6Tomomi Fujisawa7Hiroshi Ikegami8Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, JapanDepartment of Molecular Endocrinology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, JapanDepartment of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, JapanDepartment of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, JapanDepartment of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, JapanThe quantitative trait locus (QTL) mapping in segregating crosses of NSY (Nagoya-Shibata-Yasuda) mice, an animal model of type 2 diabetes, with nondiabetic strain C3H/He mice has identified diabetogenic QTLs on multiple chromosomes. The QTL on chromosome 11 (Chr11) (Nidd1n) showing the largest effect on hyperglycemia was confirmed by our previous studies with homozygous consomic mice, C3H-11NSY, in which the NSY-derived whole Chr11 was introgressed onto control C3H background genes. C3H-11NSY mice also showed a streptozotocin (STZ) sensitivity. In the present study, we constructed heterozygous C3H-11NSY mice and the phenotypes were analyzed in detail in comparison with those of homozygous C3H-11NSY and C3H mice. Heterozygous C3H-11NSY mice had significantly higher blood glucose levels and STZ sensitivity than those in C3H mice. Hyperglycemia and STZ sensitivity in heterozygous C3H-11NSY mice, however, were not as severe as in homozygous C3H-11NSY mice. The body weight and fat pad weight in heterozygous C3H-11NSY mice were similar to those in C3H and homozygous C3H-11NSY mice. These data indicated that the introgression of Chr11 of the diabetes-susceptible NSY strain onto diabetes-resistant C3H caused marked changes in the glucose tolerance and STZ susceptibility even in a heterozygous state, and suggested that the mode of inheritance of a gene or genes on Chr11 for hyperglycemia and STZ sensitivity is additive.http://dx.doi.org/10.1155/2013/608923
spellingShingle Naru Babaya
Hironori Ueda
Shinsuke Noso
Yoshihisa Hiromine
Koji Nojima
Michiko Itoi-Babaya
Misato Kobayashi
Tomomi Fujisawa
Hiroshi Ikegami
Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11
Journal of Diabetes Research
title Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11
title_full Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11
title_fullStr Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11
title_full_unstemmed Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11
title_short Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11
title_sort dose effect and mode of inheritance of diabetogenic gene on mouse chromosome 11
url http://dx.doi.org/10.1155/2013/608923
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