Establishment of a novel rat model for cystinosis

• Project/Area Number: 23500508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: OKAMURA TADASHI 独立行政法人国立国際医療研究センター, その他部局等, その他 (00333790)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Yukiko (独)国立国際医療研究センター研究所, 動物実験施設, 技術職員 (00469983)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 疾患モデル / シスチン蓄積症 / シスチノーシス / リソソーム蓄積症 / HPLC / モデルラット / (2) モデルラット / (3) HPLC

Research Abstract

Cystinosis is a rare lysosomal storage disease characterized by the abnormal accumulation of cysteine in various organs. Accumulation of cysteine in all tissues eventually leads to multisystemic disease. The causative gene, CTNS, encodes cystinosin, the lysosomal cysteine transporter. We identified a 13-bp deletion within Ctns gene in LEA rat, and have established a congenic strain carrying mutant Ctns gene from LEA rat on F344 genetic background. We also developed a simple and rapid method for determination of cysteine using HPLC to evaluate its accumulation in cells and tissues. The congenic rats lacking the function of Ctns is expected to be a useful for model animal of understanding cystinosis.

Research Products

• [Journal Article] Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes (2013)
  • Author(s): Okamura, T., Pei, XY., Miyoshi, I., Shimizu, Y., Takanashi-Yanobu, R., Mototani, Y., Takao Kanai, T., Satoh, J., Kimura, N. and Kasai, N
  • Journal Title: J Diabetes Res Volume: 2013 Pages: 986462-986462
  • DOI: 10.1155/2013/986462
  • Peer Reviewed
• [Journal Article] Serotonin regulates glucose-stimulated insulin secretion from pancreatic ß cells during pregnancy. (2013)
  • Author(s): Ohara-Imaizumi, M., Kim, H., Yoshida, M., Fujiwara, T., Aoyagi, K., Toyofuku, Y., Nakamichi, Y., Nishiwaki, C., Okamura, T., Uchida, T., Fujitani, Y., Akagawa, K., Kakei, M., Watada, H., German, M.S., and Nagamatsu, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 110 Issue: 48 Pages: 19420-19425
  • DOI: 10.1073/pnas.1310953110
  • Peer Reviewed
• [Journal Article] Quantitative assessment of pdx1 promoter activity in vivo using a secreted luciferase reporter system. (2013)
  • Author(s): Nishimura, W., Eto, K., Miki, A., Goto, M., Kawaguchi, M., Nammo, T., Udagawa, H., Hiramoto, M., Shimizu, Y., Okamura, T., Fujiwara, T., Yasuda, Y. and Yasuda, K.
  • Journal Title: Endocrinology Volume: 154 Issue: 11 Pages: 4388-4395
  • DOI: 10.1210/en.2012-2248
  • Peer Reviewed
• [Journal Article] Deletion of CDKAL1 Affects High-Fat Diet-Induced Fat Accumulation and Glucose-Stimulated Insulin Secretion in Mice, Indicating Relevance to Diabetes. (2012)
  • Author(s): Okamura T, Yanobu-Takanashi R, Takeuchi F, Isono M, Akiyama K, Shimizu Y, Goto M, Liang Y-Q, Yamamoto K, Katsuya T, Fujioka A, Ohnaka K, Takayanagi R, Ogihara T, Yamori Y, Kato N.
  • Journal Title: PLoS One Volume: 7 Issue: 11 Pages: e49055-e49055
  • DOI: 10.1371/journal.pone.0049055
  • Peer Reviewed
• [Journal Article] Simultaneous two-dimensional HPLC determination of free D-serine and D-alanine in the brain and periphery of mutant rats lacking D-amino-acid oxidase (2011)
  • Author(s): Yurika MIYOSHI, et al
  • Journal Title: Journal of Chromatography B Volume: 879 Issue: 29 Pages: 3184-3189
  • DOI: 10.1016/j.jchromb.2010.08.024
  • Peer Reviewed
• [Presentation] 新規シスチン蓄積症モデルラットの樹立 (2014)
  • Author(s): 清水有紀子, 他
  • Organizer: 第61回日本実験動物科学技術 2014
  • Place of Presentation: 札幌
• [Presentation] 新規シスチン蓄積症モデルラットの樹立 (2014)
  • Author(s): 清水有紀子、高梨理絵子、金井孝夫、岡村匡史
  • Organizer: 第61回日本実験動物科学技術2014
  • Place of Presentation: 札幌
• [Presentation] 2 型糖尿病感受性遺伝子Cdkal1の糖代謝における機能解析 (2013)
  • Author(s): 高梨理絵子, 他
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば
• [Presentation] 一体型多孔性シリカカラムを用いたシスチン定量法の開発とシスチン蓄積症モデルラットへの応用 (2012)
  • Author(s): 清水有紀子, 他
  • Organizer: 第59回日本実験動物学会総会
  • Place of Presentation: 大分
• [Presentation] 一体型多孔性シリカカラムを用いたシスチン定量法の開発とシスチン蓄積症モデルラットへの応用 (2012)
  • Author(s): 清水有紀子、矢延―高梨理絵子、金井孝夫、笠井憲雪、浜瀬健司、岡村匡史
  • Organizer: 第５９回日本実験動物学会総会
  • Place of Presentation: 別府
• [Remarks]
  • URL: http://www.rincgm.jp/department/lab/08/