Identification of the diabetogenic gene and its related genes of high fat diet-induced diabetes by using novel mouse model

• Project/Area Number: 21380079
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Nagoya University
• Principal Investigator: HORIO Fumihiko 名古屋大学, 生命農学研究科, 教授 (20165591)
• Co-Investigator(Renkei-kenkyūsha): OHNO Tamio 名古屋大学, 大学院・医学系研究科, 准教授 (90293620) ; IKEGAMI Hiroshi 近畿大学, 医学部, 教授 (20221062) ; MURAI Atsushi 名古屋大学, 大学院・生命農学研究科, 准教授 (10313975) ; KOBAYASHI Misato 名古屋大学, 大学院・生命農学研究科, 助教 (20456586)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 栄養生化学 / 糖尿病 / 糖尿病遺伝子 / 高脂肪食 / マウス

Research Abstract

SMXA-5 mouse is a novel animal model for type 2 diabetes induced by high fat diet-feeding. We have mapped the diabetic QTL (quantitative trait locus:T2dm2sa) on chromosome 2 of SMXA-5 mouse. The aim of this study is to choose the candidate gene for this diabetogenic gene and identify it as a causative gene. Simultaneously, the controlled genes by the isolated gene, which contribute to the development of diabetes,were screened.The chromosomal region which this diabetogenic gene exists was narrowed to 5Mb region of chromosome 2 by the phenotipic analyses of several diabetic congenic strains. As a candidate gene, Rapgef 4 was chosen. In the exon of Rapgef4 of SMXA-5 mouse, we observed a mutation causing the amino acid substitution. Further study is needed to clarify that this mutation of rapgef4 caused the development of diabetes.

Research Products

• [Journal Article] Establishment of consomic strains derived from A/J and SM/J mice for genetic analysis of complex traits. (2012)
  • Author(s): Ohno, T., Hata, K., Baba, T., Io, F., Kobayashi, M., Horio, F. and Nishimura, M.
  • Journal Title: Mamm.Genome Volume: 23 Pages: 764-769
  • Peer Reviewed
• [Journal Article] 2 型糖尿病動物モデルを用いた糖尿病発症因子解析の最新動向 (2012)
  • Author(s): 小林美里、堀尾文彦
  • Journal Title: 日本臨床 Volume: 70(Suppl 3) Pages: 202-206
• [Journal Article] Ternatin, a cyclic peptide isolated from mushroom, and its derivative suppress hyperglycemia and hepatic fatty acid synthesis in spontaneously diabetic KK-Ay mice (2012)
  • Author(s): M. Kobayashi, H. Kawashima, K. Takemori, H. Ito, A. Murai, S. Masuda, K. Yamada, D. Uemura, F. Horio
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 427 Issue: 2 Pages: 299-304
  • DOI: 10.1016/j.bbrc.2012.09.045
  • Peer Reviewed
• [Journal Article] 2型糖尿病動物モデルを用いた糖尿病発症因子解析の最新動向 (2012)
  • Author(s): 小林美里
  • Journal Title: 日本臨床 Volume: 70 Pages: 202-206
• [Journal Article] Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J mice fed a high-fat diet. (2011)
  • Author(s): Matsuda, Y., Kobayashi, M., Yamauchi, R.,, Ojika,. M., Hiramitsu, M., Inoue, T.,..Katagiri, T., Murai A,. and Horio, F.
  • Journal Title: Biosci.Biotechnol.Biochem Volume: 75(12) Pages: 2309-2315
  • NAID: 10030397482
  • Peer Reviewed
• [Journal Article] Coffee and Caffeine Improve Insulin Sensitivity and Glucose Tolerance in C57BL/6J Mice Fed a High-Fat Diet (2011)
  • Author(s): Matsuda, Y.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 75 Issue: 12 Pages: 2309-2315
  • DOI: 10.1271/bbb.110452
  • NAID: 10030397482
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. (2010)
  • Author(s): Yamauchi, R., Kobayashi, M., Matsuda, Y., Ojika, M., Shigeoka, S., Yamamoto, Y., Tou, Y., Inoue, T., Katagiri, T., Murai, A. and Horio, F
  • Journal Title: J.Agric.Food Chem Volume: 58 Pages: 5597-5603
  • Peer Reviewed
• [Journal Article] Genetic analysis of abdominal fat distribution in SM/J and A/J mice. (2010)
  • Author(s): Kobayashi, M., Ohno, T., Hada, N., Fujiyoshi,M., Kuga, M., Nishimura, M., Murai, A. andHorio, F.
  • Journal Title: J.Lipid Res. Volume: 51 Pages: 3463-3469
  • Peer Reviewed
• [Journal Article] Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. (2010)
  • Author(s): Yamauchi, R., Kobayashi, M., Matsuda, Y., Ojika, M., Shigeoka, S., Yamamoto, Y., Tou, Y., Inoue, T., Katagiri, T., Murai, A.,Horio, F.
  • Journal Title: J.Agric.Food Chem. Volume: 58 Pages: 5597-5603
  • Peer Reviewed
• [Journal Article] 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. (2009)
  • Author(s): Kobayashi, M., Hada, N., Hoshino, H., Ozawa, T., Umeshita, K., Nishimura, M., Murai, A., Ohno, T. and Horio, F
  • Journal Title: J.Nutr.Sci.Vitaminol. Volume: 55 Pages: 257-263
  • NAID: 10025971398
  • Peer Reviewed
• [Journal Article] Body and major organ weights of A/J-Chr 11(SM) consomic mice. (2009)
  • Author(s): Tanaka, S., Mizorogi, T., Nishijima, K., Kuwahara, S., Tsujio, M., Aoyama, H., Taguchi, C., Kobayashi, M., Horio, F. and Ohno, T
  • Journal Title: Exp.Anim. Volume: 58 Pages: 357-36
  • NAID: 130000122242
  • Peer Reviewed
• [Presentation] マウス第12番染色体上の脂肪肝感受性に関与する遺伝子の探索 (2013)
  • Author(s): 小林美里、立石壮志、都築佳奈、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 日本農芸化学会 2012年度大会
  • Place of Presentation: 京 都
  • Year and Date: 2013-03-23
• [Presentation] 脂肪肝感受性を規定する候補遺伝子の肝細胞脂質代謝に対する作用の解析 (2012)
  • Author(s): 都築佳奈、小林美里、鈴木 京、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 日本農芸化学会 2013年度大会
  • Place of Presentation: 仙 台
  • Year and Date: 2012-03-26
• [Presentation] SMXA-5マウスが有する脂肪肝感受性遺伝子座(Fllsa)の候補遺伝子の検討 (2011)
  • Author(s): 立石壮志、小林美里、都築佳奈、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 日本農芸化学会2011年度大会(京都)2011.3
  • Place of Presentation: 要旨集
  • Year and Date: 2011-03-05
• [Presentation] SMXA-5 マウスが有する脂肪肝感受性遺伝子座(Fl1sa)の候補遺伝子の検討 (2011)
  • Author(s): 立石壮志、小林美里、都築佳奈、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 日本農芸化学会 2011 年度大会
  • Place of Presentation: 京都
• [Presentation] マウス第12 番染色体上に存在する脂肪肝感受性遺伝子座の候補遺伝子の解析 (2011)
  • Author(s): 小林美里、立石壮志、都築佳奈、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 第65回日本栄養・食糧学会大会
  • Place of Presentation: 東京
• [Presentation] SMXA-5 マウスの脂肪肝感受性遺伝子座の候補遺伝子 (2011)
  • Author(s): 立石壮志、小林美里、都築佳奈、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 2011 年度日本農芸化学会関西支部・中部支部合同大会
  • Place of Presentation: 京都
• [Presentation] マウス第12 番染色体に存在する脂肪肝感受性遺伝子の遺伝子発現解析による探索 (2010)
  • Author(s): 小林美里、田口千恵、立石壮志、村井篤嗣、大野民生、堀尾文彦
  • Organizer: 日本農芸化学会 2010 年度大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] マウス 12 番染色体に存在する脂肪肝感受性遺伝子座の解析 (2010)
  • Author(s): 小林美里、田口千恵、立石壮志、村井篤嗣、大野民生、堀尾文彦
  • Organizer: 日本糖尿病・肥満動物学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-01-22
• [Presentation] 高脂肪食性脂肪肝の感受性遺伝子座(Fl1sa)の肥満・糖代謝に対する作用:コンソミックマウスでの解析 (2010)
  • Author(s): 小林美里、田口千恵、立石壮志、大野民生、村井篤嗣、堀尾文彦
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島
• [Presentation] マウス第１２番染色体上の脂肪肝感受性に関与する遺伝子の探索
  • Author(s): 小林美里
  • Organizer: 日本農芸化学会２０１２年度大会
  • Place of Presentation: 京都
• [Presentation] 高脂肪食誘発型２型糖尿病の原因遺伝子の解析 －新規モデルマウスを用いて－
  • Author(s): 堀尾文彦
  • Organizer: 第６６回日本栄養・食糧学会大会
  • Place of Presentation: 仙台
  • Invited
• [Book] ビタミン総合事典、日本ビタミン学会編集 (2010)
  • Author(s): 堀尾文彦(分担執筆)
  • Publisher: 朝倉書店
• [Book] ダイズの全て(喜多村啓介, ら編) (2010)
  • Author(s): 堀尾文彦(分担執筆)
  • Publisher: サイエンスフォーラム
• [Remarks]
  • URL: http://www.agr.nagoya-u.ac.jp/~anutr/