The development of novel and useful mouse models for kidney diseases

2013 Fiscal Year Final Research Report

• Project/Area Number: 23700522
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: UCHIO Kozue 独立行政法人医薬基盤研究所, 難病・疾患資源研究部, 主任研究員 (70373397)
• Project Period (FY): 2011 – 2013
• Keywords: 実験動物学 / 腎疾患

Research Abstract

The number of patients with chronic kidney diseases (CKD) is expected to increase steadily each year in Japan. It has not been reported the effective therapy for renal insufficiency except dialysis and transplantation. The mechanisms responsible for CKD have not been made clear yet, so that it is difficult to discover effective drugs for kidney diseases. One of the reasons for the difficulties is that suitable animal models for various kidney diseases don't exist. Therefore, in this study, I tried to find the causal genes responsible for the progression of kidney diseases and to male a novel and suitable mouse model for kidney diseases. QTL and DNA array analyses using ICGN mice, a nephrotic syndrome model, revealed that some genomic loci responsible for the progression of kidney diseases. I developed congenic mice carrying these genomic loci, and analyzed the phenotype. These strains might contributed to elucidate the mechanisms responsible for kidney diseases.

Research Products

• [Journal Article] Tenc1 Deficient Mice Develop Glomerular Disease in a Strain-Specific Manner (2013)
  • Author(s): Uchio-Yamada K., Sawada K., Tamura K., Katayama S., Monobe Y., Yamamoto Y., Ogura A., Manabe N.
  • Journal Title: Nephron Experimental Nephrology Volume: 123 Pages: 22-33
• [Journal Article] Gene Expression Analysis Detected Low Expression Level of C1s Gene in ICR-derived Glomerulonephritis (ICGN) Mice (2013)
  • Author(s): Tamura K., Uchio-Yamada K., Manabe N. Noto T., Hirota R., Unami A., Matsumoto M., Miyamae Y.
  • Journal Title: Nephron Experimental Nephrology Volume: 123 Pages: 34-45
• [Journal Article] Zygosity Determination in Hairless Mice by PCR Based on Hr(hr) Gene Analysis (2013)
  • Author(s): Suzuki O, Koura M, Noguchi Y, Uchio-Yamada K, Matsuda J
  • Journal Title: Exp Anim. Volume: 62(3) Pages: 267-273
• [Journal Article] Protein kinase C regulates human pluripotent stem cell self-renewal (2013)
  • Author(s): Kinehara M, Kawamura S, Tateyama D, Suga M, Matsumura H, Mimura S, Hirayama N, Hirata M, Uchio-Yamada K, Kohara A, Yanagihara K, Furue MK
  • Journal Title: PLoS One Volume: 8(1) Pages: e54122
• [Journal Article] Oral glucose loading modulates plasma β-amyloid level in alzheimer's disease patients : potential diagnostic method for Alzheimer's disease (2012)
  • Author(s): Takeda S, Sato N, Uchio-Yamada K, Yu H, Moriguchi A, Rakugi H, Morishita R
  • Journal Title: Dement Geriatr Cogn Disord. Volume: 34(1) Pages: 25-30
• [Journal Article] ICR系マウスの遺伝子資源としての有用性 (2012)
  • Author(s): 山本美江、内尾 -山田こずえ、高野薫、小倉淳郎、浅野敏彦、中川雅郎
  • Journal Title: 岡山実験動物研究会会報 Volume: 第28号 Pages: 59-62
• [Journal Article] Role of insulin signaling in the interaction between Alzheimer disease and diabetes mellitus : a missing link to therapeutic potential (2011)
  • Author(s): Sato N, Takeda S, Uchio-Yamada K, Ueda H, Fujisawa T, Rakugi H, Morishita R.
  • Journal Title: Current Aging Science Volume: 4(2) Pages: 118-127
• [Journal Article] Use of sample mixtures for standard curve creation in quantitative western blots (2011)
  • Author(s): Suzuki O, Koura M, Noguchi Y, Uchio-Yamada K, Matsuda J
  • Journal Title: Exp Anim. Volume: 60(2) Pages: 193-196
• [Journal Article] Adult onset cardiac dilatation in a transgenic mouse line with Galβ1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes : a new model for dilated cardiomyopathy (2011)
  • Author(s): Suzuki O, Kanai T, Nishikawa T, Yamamoto Y, Noguchi A, Takimoto K, Koura M, Noguchi Y, Uchio-Yamada K, Tsuji S, Matsuda J
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci. Volume: 87(8) Pages: 550-562
• [Journal Article] A Potent Inhibitor of SIK2, 3, 3', 7-Trihydroxy-4'-Methoxyflavon (4'-O-Methylfisetin), Promotes Melanogenesis in B16F10 Melanoma Cells (2011)
  • Author(s): Kumagai A, Horike N, Satoh Y, Uebi T, Sasaki T, Itoh Y, Hirata Y, Uchio-Yamada K, Kitagawa K, Uesato S, Kawahara H, Takemori H, Nagaoka Y
  • Journal Title: PLoS One Volume: 6(10) Pages: e26148
• [Presentation] Abeta is prerequisite. But insufficient to cause tau phosphorylatic in vivo : Tau phosphorylation in APP mice by diabetes (2013)
  • Author(s): 里直行、森-植田茉莉、田中稔久、澤口翔伍、向園昌弘、武田朱公、篠原充、村山繁雄、内尾-山田こずえ、上田裕紀、武田雅俊、樂木宏実、森下竜一
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 20131203-07
• [Presentation] 食餌誘導性肥満マウスにおける畜肉食あるいは魚食が代謝に及ぼす影響 (2013)
  • Author(s): 河原崎正貴、矢口文、千葉洋祐、鎌田彰、小泉大輔、島田昌彦、内尾こずえ、根本直
  • Organizer: 第8回メタボボロームシンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 20131003-04
• [Presentation] 食餌誘導性肥満マウスにおける畜肉食あるいは魚食が代謝に及ぼす影響 (2013)
  • Author(s): 河原崎正貴、矢口文、千葉洋祐、鎌田彰、小泉大輔、島田昌彦、内尾こずえ、根本直
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 20130524-26
• [Presentation] 糖尿病はアルツハイマー病における恒常性維持機構を破綻させる (2013)
  • Author(s): 里直行、森 -植田茉莉、田中稔久、武田朱公、向園昌弘、澤口翔伍、内尾-山田こずえ、篠原充、村山繁雄、武田雅俊、樂木宏実、森下竜一
  • Organizer: 第32回日本認知症学会学術集会
  • Place of Presentation: 松本
  • Year and Date: 2013-11-09
• [Presentation] Possible involvements of Abeta, insulin signaling and tau phosphorylation in the pathological interaction between Alzheimer disease and diabetes (2013)
  • Author(s): Sato N, Mori-Ueda M, Tanaka T, Takeda S, Uchio-Yamada K, Ueda H, Shinohara M, Murayama S, Takeda M, Rakugi H, Morishita R
  • Organizer: AAIC 2013 The Alzheimer's Association International Conference 2013
  • Place of Presentation: Boston
  • Year and Date: 2013-07-14
• [Presentation] 糖尿病はAPPトランスジェニックマウス脳においてタウのリン酸化を促進する (2012)
  • Author(s): 里直行、森-植田茉莉、田中稔久、武田朱公、内尾 -山田こずえ、篠原充、村山繁雄、武田雅俊、樂木宏実、森下竜一
  • Organizer: 第31回日本認知症学会学術集会
  • Place of Presentation: つくば
  • Year and Date: 20121026-28
• [Presentation] Roles of beta-amyloid and insulin resistance in the interaction between diabetes mellitus and Alzheimer's disease (2012)
  • Author(s): Sato N, Mori-Ueda M, Tanaka T, Takeda S, Uchio-Yamada K, Ueda H, Shinohara M, Murayama S, Takeda M, Rakugi H, Morishita R
  • Organizer: Gordon Research Conferences, Neurobiology of Brain (Disorders Chair: Jie Shen, Vice Chair: Joachim J. Herz)
  • Place of Presentation: Stonehill College
  • Year and Date: 20120805-10
• [Presentation] アルツハイマー病APP Tgマウス脳における糖尿病によるタウ・リン酸化の促進 (2012)
  • Author(s): 里直行、森-植田茉莉、田中稔久、武田朱公、内尾 -山田こずえ、篠原充、村山繁雄、武田雅俊、樂木宏実、森下竜一
  • Organizer: 脳心血管抗加齢研究会2012
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-18
• [Presentation] 糖負荷試験における血中βアミロイド測定―アルツハイマー病診断補助方法としての可能性 (2012)
  • Author(s): 里直行、武田朱公、内尾-山田こずえ、湯久浩、守口篤、樂木宏実、森下竜一
  • Organizer: 脳心血管抗加齢研究会2012
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-18
• [Presentation] The mechanisms by which diabetes mellitus increases the risk of Alzheimer's disease (2012)
  • Author(s): Sato N, Mori-Ueda M, Tanaka T, Takeda S, Uchio-Yamada K, Ueda H, Shinohara M, Murayama S, Takeda M, Rakugi H, Morishita R
  • Organizer: Keystone Symposia, Aging and Diseases of Aging
  • Place of Presentation: Tokyo
  • Year and Date: 2012-10-25
• [Presentation] Old APPxob/ob mice showed highly increased level of tau phosphorylation in brain (2012)
  • Author(s): Sato N, Mori-Ueda M, Tanaka T, Takeda S, Uchio-Yamada K, Ueda H, Shinohara M, Murayama S, Takeda M, Rakugi H, Morishita R
  • Organizer: Neuroscience 2012
  • Place of Presentation: New Orleans
  • Year and Date: 2012-10-15
• [Presentation] 糖尿病によるアルツハイマー病トランスジェニックマウス脳におけるタウのリン酸化の促進 (2012)
  • Author(s): 里直行、森-植田茉莉、田中稔久、武田朱公、内尾-山田こずえ、篠原充、村山繁雄、武田雅俊、樂木宏実、森下竜一
  • Organizer: VAS-COG JAPAN 2012
  • Place of Presentation: 東京
  • Year and Date: 2012-09-09
• [Presentation] 糖負荷後血中Aβ値の変動とそのアルツハイマー病診断指標としての応用 (2012)
  • Author(s): 武田朱公、里直行、内尾-山田こずえ、湯久浩、守口篤、樂木宏実、森下竜一
  • Organizer: VAS-COG JAPAN 2012
  • Place of Presentation: 東京、 YIA(臨床部門)
  • Year and Date: 2012-09-08
• [Presentation] Change in plasma beta-amyloid level after glucose loading : a possible biomarker for Alzheimer Disease (2011)
  • Author(s): Sato N, Takeda S, Ueda M, Yu H, Moriguchi A, Uchio-Yamada K, Rakugi H, Morishita R
  • Organizer: AAIC (Alzheimer Association International Conference) 2011
  • Place of Presentation: Paris
  • Year and Date: 2011-07-18
• [Presentation] アルツハイマー病と糖尿病の相互的病態修飾 (2011)
  • Author(s): 里直行、武田朱公、内尾-山田こずえ、樂木宏実、森下竜一
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-21
• [Presentation] 糖尿病がアルツハイマー病の後天的危険因子である機序 (2011)
  • Author(s): 里直行、武田朱公、内尾-山田こずえ、樂木宏実、森下竜一
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-19
• [Presentation] Alteration in Plasma Beta-amyloid Levels after Glucose Loading Could Be a Novel Diagnostic Marker for Alzheimer Disease (Poster session 1) (2011)
  • Author(s): Takeda S, Sato N, Uchio-Yamada K, Yu H, Moriguchi A, Rakugi H, Morishita R
  • Organizer: The 10th International Conference on Alzheimer's and Parkinson's Diseases (ADPD 2011)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2011-03-09
• [Presentation] 糖負荷による血中Aβの変動を利用した新たなアルツハイマー病診断指標の探索 : 全身糖代謝が血中 Aβ濃度に与える影響の検討(ポスター) (2010)
  • Author(s): 武田朱公、里直行、内尾こずえ、澤田京子、國枝孝典、篠原充、楽木宏実、森下竜一
  • Organizer: 第10回日本抗加齢医学会総会、ポスターセッション:脳・神経 1(P165)
  • Place of Presentation: 京都
  • Year and Date: 2010-06-12
• [Remarks] 原発性ネフローゼマウスの解析
  • URL: http://animal.nibio.go.jp/research/j_icgn_research.html
• [Remarks] マウス標準系統プロファイリング
  • URL: http://animal.nibio.go.jp/research/j_profiling.html
• [Remarks] ICGNマウス詳細データ
  • URL: http://animal.nibio.go.jp/j_icgnmouse.html