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To developtherapeutic and prophylactic procedures for citrin deficiency

Research Project

Project/Area Number 24591516
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKumamoto University

Principal Investigator

SAHEKI Takeyori  熊本大学, 生命資源研究・支援センター, 特任教授 (10056070)

Co-Investigator(Kenkyū-buntansha) USHIKAI Miharu  鹿児島大学, 医歯学総合研究科, 助教 (70232816)
Co-Investigator(Renkei-kenkyūsha) YAMAMURA Ken-ichi  熊本大学, 生命資源研究・支援センター, 教授 (90115197)
OSHIMURA Mitsuo  鳥取大学, 大学院医学系研究科, 教授 (20111619)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsシトリン欠損症 / マウスモデル / 糖質毒性 / アスパラギン酸グルタミン酸ミトコンドリア膜輸送体 / ピルビン酸ナトリウム / アミノ酸 / グリセロール3-リン酸 / グリセロール
Outline of Final Research Achievements

By using a citrin deficiency model mouse, we have got following results in the field of pathophysiology and treatment. (1) Urine glycerol level was higher in the model mouse than in the control mice and sucrose administration increased plasma glycerol in the model mouse, suggesting that these parameters are possible diagnostics. (2) Aversion to the high concentration of sucrose, ethanol and glycerol, the precipitating factors of adult-onset type II citrullinemia (CTLN2), was observed in the model mouse, and the forced oral administration of such solutions coincidentally accompanied with both a marked increase in hepatic glycerol 3-phosphate and a decrease in ATP. These results suggest that substances which suppress the phenomena stated above (an increase in glycerol 3-phosphate and a decrease in ATP) are possible therapeutics for citrin deficiency.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (38 results)

All 2015 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 10 results) Presentation (20 results) (of which Invited: 10 results) Book (3 results) Remarks (3 results)

  • [Journal Article] Screening for five prevalent mutations of SLC25A13 gene in Guangdong, China: a molecular epidemiologic survey of citrin deficiency.2014

    • Author(s)
      Zhang ZH, Yang ZG, Chen FP, Kikuchi A, Liu ZH, Kuang LZ, Li WM, Song YZ, Kure S, Saheki T.
    • Journal Title

      Tohoku J Exp Med.

      Volume: 233 Pages: 275-281

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytosolic reducing power preserves glutamate in retina2013

    • Author(s)
      Du J, Cleghorn W, Contreras L, Linton JD, Chan GC, Chertov AO, Saheki T, Govindaraju V, Sadilek M, Satrustegui J, Hurley JB.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110 Issue: 46 Pages: 18501-18506

    • DOI

      10.1073/pnas.1311193110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China.2013

    • Author(s)
      Song YZ, Zhang ZH, Lin WX, Zhao XJ, Deng M, Ma YL, Guo L, Chen FP, Long XL, He XL, Sunada Y, Soneda S, Nakatomi A, Dateki S, Ngu LH, Kobayashi K, Saheki T.
    • Journal Title

      PLoS One.

      Volume: 8 Issue: 9 Pages: e74544-e74544

    • DOI

      10.1371/journal.pone.0074544

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons.2013

    • Author(s)
      Llorente-Folch I, Rueda CB, Amigo I, del Arco A, Saheki T, Pardo B, Satrústegui J.
    • Journal Title

      J Neurosci.

      Volume: 33 Issue: 35 Pages: 13957-13971

    • DOI

      10.1523/jneurosci.0929-13.2013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Different regional distribution of SLC25A13 mutations in Chinese patients with neonatal intrahepatic cholestasis.2013

    • Author(s)
      Chen R, Wang XH, Fu HY, Zhang SR, Abudouxikuer K, Saheki T, Wang JS.
    • Journal Title

      World J Gastroenterol.

      Volume: 19 Issue: 28 Pages: 4545-4551

    • DOI

      10.3748/wjg.v19.i28.4545

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A 73-year-old patient with adult-onset type II citrullinemia successfully treated by sodium pyruvate and arginine.2013

    • Author(s)
      Yazaki M, Kinoshita M, Ogawa S, Fujimi S, Matsushima A, Hineno A, Tazawa K, Fukushima K, Kimura R, Yanagida M, Matsunaga H, Saheki T, Ikeda S.
    • Journal Title

      Clin Neurol Neurosurg.

      Volume: 115 Issue: 8 Pages: 1542-1545

    • DOI

      10.1016/j.clineuro.2012.12.027

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] AGC1-malate aspartate shuttle activity is critical for dopamine handling in the nigrostriatal pathway2013

    • Author(s)
      Llorente-Folch I, Sahun I, Contreras L, Casarejos MJ, Grau JM, Saheki T, Mena MA, Satrustegui J, Dierssen M, Pardo B.
    • Journal Title

      J Neurochem

      Volume: 124 Issue: 3 Pages: 347-362

    • DOI

      10.1111/jnc.12096

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simple and rapid genetic testing for citrin deficiency by screening 11 prevalent mutations in SLC25A132012

    • Author(s)
      Kikuchi A, Arai-Ichinoi N, Sakamoto O, Matsubara Y, Saheki T, Kobayashi K, Ohura T, Kure S
    • Journal Title

      Mol Genet Metab

      Volume: 105(4) Issue: 4 Pages: 553-8

    • DOI

      10.1016/j.ymgme.2011.12.024

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of supplementation on food intake, body weight and hepatic metabolites in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse model of human citrin deficiency2012

    • Author(s)
      Saheki T, Inoue K, Ono H, Katsura N, Yokogawa M, Yoshidumi Y, Furuie S, Kuroda E, Ushikai M, Asakawa A, Inui A, Eto K, Kadowaki T, Sinasac DS, Yamamura K, Kobayashi K
    • Journal Title

      Mol Genet Metab

      Volume: 107(3) Issue: 3 Pages: 322-9

    • DOI

      10.1016/j.ymgme.2012.07.021

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biochemical characteristics of neonatal cholestasis induced by citrin deficiency.2012

    • Author(s)
      Wang JS
    • Journal Title

      World J Gastroenterol

      Volume: 18 Issue: 39 Pages: 5601-5607

    • DOI

      10.3748/wjg.v18.i39.5601

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] シトリン欠損症2012

    • Author(s)
      佐伯武頼
    • Journal Title

      小児内科

      Volume: 44 Pages: 148-149

    • NAID

      10024461636

    • Related Report
      2012 Research-status Report
  • [Journal Article] アミノ酸代謝異常症-シトリン欠損症2012

    • Author(s)
      佐伯武頼
    • Journal Title

      小児内科

      Volume: 44 Pages: 1623-1627

    • Related Report
      2012 Research-status Report
  • [Presentation] Pathophysiology of citrin deficiency and current progress on its treatment2015

    • Author(s)
      Takeyori Saheki, Yuki Fujimoto, Sumie Furuie, Ken-ichi Yamamura, Masahide Yazaki, Shu-ichi Ikeda
    • Organizer
      Asia Conference on Inhertited Metabolic Disease (ACIMD) 2015
    • Place of Presentation
      台湾(台北)
    • Year and Date
      2015-03-20 – 2015-03-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Metabolic basis of carbohydrate toxicity in citrin, liver-type mitochondrial aspartate glutamate carrier, deficiency2015

    • Author(s)
      Saheki T, Fujimoto Y, Furuie S, Yamamura K,
    • Organizer
      Asia Europe Workshop on Inborn Error of Metabolism (AEWIEM) 2015
    • Place of Presentation
      エジプト(カイロ)
    • Year and Date
      2015-01-18 – 2015-01-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] シトリン欠損症の病態解析と治療法の開発:現在の課題2014

    • Author(s)
      佐伯武頼、藤本侑希、古家澄江、山村研一
    • Organizer
      第56回日本先天代謝異常学会・第12回アジア先天代謝異常症シンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-13 – 2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Advances in Diagnosis and Treatment of Citrin Deficiency2014

    • Author(s)
      Takeyori Saheki
    • Organizer
      International Conference on Neonatal Nutrition Support and Inherited Metabolic Disease Screening
    • Place of Presentation
      中国(広州)
    • Year and Date
      2014-10-11 – 2014-10-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Prenary session, History and fundamental basis of the pathophysiology, International Symposium on Citrin Deficiency,2014

    • Author(s)
      Takeyori Saheki
    • Organizer
      International Symposium on Citrin Deficiency
    • Place of Presentation
      中国(広州)
    • Year and Date
      2014-06-06 – 2014-06-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 特別講演「シトリン欠損症における特異な食癖とその病因・病態・治療との関連」2014

    • Author(s)
      佐伯武頼
    • Organizer
      日本栄養改善学会四国支部学術総会
    • Place of Presentation
      徳島
    • Year and Date
      2014-05-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] モデルマウスを用いたシトリン欠損症における糖質毒性の解析2014

    • Author(s)
      佐伯 武頼,藤本 侑希,山村 研一,井上 加奈子,小野 裕美
    • Organizer
      第17回日本病態栄養学会年次学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] Studies on Citrin Deficiency and Carnitine Deficiency using Animal Models.2013

    • Author(s)
      Saheki, Takeyori
    • Organizer
      Conference on Genetic and Metabolic Disease in Fujian
    • Place of Presentation
      Fujian, China
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Citrin Deficiency: Discovery of the causative gene, analysis of pathophysiology and its clinical aspects.2013

    • Author(s)
      Saheki, Takeyori
    • Organizer
      3rd ACIMD/55th JSIMD
    • Place of Presentation
      Maihama, Japan
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Plasma glycerol was increased parallel to blood ammonia in citrin deficiency model in response to administration of sugars2013

    • Author(s)
      Saheki T, Fujimoto Y, Yamamura K
    • Organizer
      3rd ACIMD/55th JSIMD
    • Place of Presentation
      Maihama, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] A possible diagnostic for citrin deficiency; high plasma and urinary glycerol detected in the model, Citrin/ mGPD double-KO mouse2013

    • Author(s)
      Fujimoto Y, Yano K, Yamashita K, Rikimaru S, Inoue K, Yamamura K, Saheki T
    • Organizer
      3rd ACIMD/55th JSIMD
    • Place of Presentation
      Maihama, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] シトリン欠損症における糖とアミノ酸の代謝異常相関2013

    • Author(s)
      佐伯武頼
    • Organizer
      日本アミノ酸学会第7回学術大会
    • Place of Presentation
      熊本市
    • Related Report
      2013 Research-status Report
  • [Presentation] モデルマウスを用いるシトリン欠損症患者の糖質忌避の機構解析2013

    • Author(s)
      佐伯武頼,藤本侑希,古家澄江,山村研一
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] Treatment of Citrin Deficiency: Assessment by using an Animal Model.2012

    • Author(s)
      Saheki T
    • Organizer
      The 2nd Asian Congress on Inherited Metabolic Disease (ACIMD) & the 12th Asia Europe Workshop on Inborn Error of Metabolism (AEWIEM),
    • Place of Presentation
      ソウル(韓国)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Citrin Deficiency -one of the most prevalent inherited metabolic diseases in East Asia-2012

    • Author(s)
      Saheki T
    • Organizer
      Vietnamese Association of Diabetes and Endocrinology
    • Place of Presentation
      フエ(ベトナム)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Citrin deficiency past, present and future -What is citrin deficiency and what should we do now?-2012

    • Author(s)
      Saheki T
    • Organizer
      12th Chinese Society of Pediatric Endocrinology and Metabolism Conference (Tongli)
    • Place of Presentation
      同里(中国)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Citrin Deficiency: Then and Now; A tribute to Dr. Keiko Kobayashi2012

    • Author(s)
      Saheki T
    • Organizer
      10th Asia-Pacific Conference on Human Genetics (APCHG)
    • Place of Presentation
      クアラルンプール(マレーシア)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 鹿児島大学医歯学総合研究科分子病態生化学において解析した尿素サイクル関連異常症例.2012

    • Author(s)
      佐伯武頼
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      じゅうろくプラザ(岐阜県)
    • Related Report
      2012 Research-status Report
  • [Presentation] CTLN2発症に関わる遺伝要因の検索:ミトコンドリアglycerol 3-phosphate dehydrogenase.2012

    • Author(s)
      佐伯武頼
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      じゅうろくプラザ(岐阜県)
    • Related Report
      2012 Research-status Report
  • [Presentation] シトリン欠損症の病態解析と治療法の開発-ピルビン酸ナトリウムの効果-

    • Author(s)
      佐伯武頼
    • Organizer
      ビタミンB研究協議会
    • Place of Presentation
      湘南国際村センター(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Book] Animal models of enhanced oxidative stress” (especially murine model of human citrin deficiency)2014

    • Author(s)
      Takeyori Saheki
    • Total Pages
      24
    • Publisher
      Springer Science and Business Media
    • Related Report
      2014 Annual Research Report
  • [Book] Oxidative Stress in Applied Basic Research and Clinical Practice - Pediatric Disorders2014

    • Author(s)
      Takeyori Saheki
    • Total Pages
      24
    • Publisher
      Springer Science and Business Media
    • Related Report
      2013 Research-status Report
  • [Book] 先天代謝異常ハンドブック2012

    • Author(s)
      佐伯武頼
    • Total Pages
      2
    • Publisher
      中山書店
    • Related Report
      2012 Research-status Report
  • [Remarks] 山村プロジェクト研究室(熊本大学生命資源研究支援センター)

    • URL

      http://irda-genetics.kuma-u.jp/yamamura/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 熊本大学資源研究・支援センター疾患モデル分野研究業績

    • URL

      http://irda-genetics.kuma-u.jp/publication/p02.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 熊本大学生命資源研究・支援センター疾患モデル分野

    • URL

      http://irda-genetics.kuma-u.jp/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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