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2011 Fiscal Year Final Research Report

Toxicity of sugars and identification of markers for pathophysiology in citrin deficiency leading to development of novel therapeutics

Research Project

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Project/Area Number 21591337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKumamoto University (2011)
Tokushima Bunri University (2009-2010)

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) KOBAYASHI Keiko  鹿児島大学, 大学院・医歯学総合研究科, 准教授 (70108869)
Project Period (FY) 2009 – 2011
Keywordsシトリン / 成人発症II型シトルリン血症(CTLN2) / 新生児肝内胆汁うっ滞症(NICCD) / マウスモデル / 糖質毒性 / メタボローム解析
Research Abstract

We have established a model mouse of citrin deficiency causing neonatal intrahepatic cholestasis(NICCD) at neonatal period and adult-onset type II citrullinemia(CTLN2) at adult age. We showed that administration of sugars to the mice caused deterioration such as hyperammonemia. From the metabolomics analysis, we found that administration of sugars induced a marked increase in hepatic glycerol-3-phosphate(G3P), which is useful as a biomarker for citrin deficiency. We found that dietary change from high protein to low protein induced a decreased body weight, mimicking growth retardation or skinniness in the disease and that addition of substance such as protein, amino acids, pyruvate and medium-chain triglyceride to the low-protein diet increased food intake and body weight.

  • Research Products

    (17 results)

All 2012 2011 2010 2009 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (5 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Simple and rapid genetic testing for citrin deficiency by screening 11 prevalent mutations in SLC25A132011

    • 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) Pages: 553-8

    • URL

      http://dx.doi.org/10.1016/j.ymgme

    • Peer Reviewed
  • [Journal Article] The characteristics of food intake in patients with type II citrullinemia. The characteristics of food intake in patients with type II citrullinemia2011

    • Author(s)
      Nakamura M, Yazaki M, Kobayashi Y, Fukushima K, Ikeda S, Kobayashi K, Saheki T, Nakaya Y
    • Journal Title

      J Nutr Sci Vitaminol(Tokyo)

      Volume: 57(3) Pages: 239-45

    • URL

      https://www.jstage.jst.go.jp/article/jnsv/57/3/57_3_239/_article

    • Peer Reviewed
  • [Journal Article] Metabolomic analysis reveals hepatic metabolite perturbations in citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mice, a model of human citrin deficiency2011

    • Author(s)
      Saheki T, 11名、Kobayashi K.(13番目)
    • Journal Title

      Mol Genet Metab

      Volume: 104(4) Pages: 492-500

    • URL

      http://dx.doi.org/10.1016/j.ymgme

    • Peer Reviewed
  • [Journal Article] Genotypic and phenotypic features of citrin deficiency : five-year experience in a Chinese pediatric center2011

    • Author(s)
      Song YZ, Deng M, Chen FP, Wen F, Guo L, Cao SL, Gong J, Xu H, Jiang GY, Zhong L, Kobayashi K, Saheki T, Wang ZN
    • Journal Title

      Int J Mol Med

      Volume: 28(1) Pages: 33-40

    • DOI

      doi:10.3892/ijmm

    • Peer Reviewed
  • [Journal Article] The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia2011

    • Author(s)
      Fu HY, Zhang SR, Wang XH, Saheki T, Kobayashi K, Wang JS
    • Journal Title

      J Gastroenterol

      Volume: 46(4) Pages: 510-8

    • DOI

      DOI:10.1007/s00535-010-0329-y

    • Peer Reviewed
  • [Journal Article] Citrin deficiency and current treatment concepts2010

    • Author(s)
      Saheki T, Inoue K, Tushima A, Mutoh K, Kobayashi K
    • Journal Title

      Mol Genet Metab

      Volume: 100 Pages: 59-64

    • DOI

      10.1016/j.ymgme.2010.02.014

    • Peer Reviewed
  • [Journal Article] Conventional diet therapy for hyperammonemia is risky in the treatment of hepatic encephalopathy associated with citrin deficiency2010

    • Author(s)
      Fukushima K, Yazaki M, Nakamura M, Tanaka N, Kobayashi K, Saheki T, Takei H, Ikeda S
    • Journal Title

      Intern Med

      Volume: 49 Pages: 243-7

    • DOI

      DOI:10.2169/internalmedicine

    • Peer Reviewed
  • [Journal Article] Neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD) as a cause of liver disease in infants in the UK2009

    • Author(s)
      Hutchin T, 6名, Kobayashi K, Saheki T.(9番目), 他2名
    • Journal Title

      J Inherit Metab Dis

      Volume: 11

    • Peer Reviewed
  • [Journal Article] Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period2009

    • Author(s)
      Nagasaka H, 6名、Kobayashi K, Saheki T(9番目), 他2名
    • Journal Title

      Mol Genet Metab

      Volume: 97 Pages: 21-6

    • DOI

      10.1016/j.metabol

    • Peer Reviewed
  • [Journal Article] Neonatal intrahepatic cholestasis caused by citrin deficiency : clinical and laboratory investigation of 13 subjects in mainland of China2009

    • Author(s)
      Song YZ, 8名, Kobayashi K, Saheki T(11番目), Zheng XY
    • Journal Title

      Dig Liver Dis

      Volume: 41(9) Pages: 683-9

    • DOI

      10.1016/j.dld.2008.11.014

    • Peer Reviewed
  • [Presentation] Overview of Citrin Defciiency : Pathophysiology and therapy for citrin deficincy based on the mouse model analysis2011

    • Author(s)
      T. Saheki, K. Kobayashi
    • Organizer
      International Symposium on Citrin Deficiency at Matsumoto(招待講演)
    • Place of Presentation
      ホテルブエナビスタ、長野
    • Year and Date
      2011-10-06
  • [Presentation] Citrin deficiency : Pathophysiology, treatment and mouse model2011

    • Author(s)
      T. Saheki
    • Organizer
      9th International Conference on Amino Acids, Peptides and Proteins
    • Place of Presentation
      北京(中国)
    • Year and Date
      2011-08-03
  • [Presentation] CITRIN DEFICIENCY : PATHOPHYSIOLOGY AND TREATMENT BASED ON ANIMAL MODEL ANALYSIS2010

    • Author(s)
      Saheki T, Inoue K, Ono H, Katsura N, Yokogawa M, Yoshidumi Y, Kobayashi K
    • Organizer
      9th Asia Pacific Conference on Human Genetics
    • Place of Presentation
      Hong Kong(china)
    • Year and Date
      2010-12-02
  • [Presentation] Plenary Lecture Pathophysiology and therapy of citrin deficiency : consideration from analysis of the model mice2010

    • Author(s)
      Saheki T, Kobayashi K
    • Organizer
      The 1st Asian Congress for Inherited Metabolic Diseases
    • Place of Presentation
      福岡国際会議場, Fukuoka
    • Year and Date
      2010-03-09
  • [Presentation] Citrin deficiency and current treatment concepts2009

    • Author(s)
      Saheki T., Kobayashi K.
    • Organizer
      Satellite Symposium to the 11th International Congress on Inborn Errors of Metabolism
    • Place of Presentation
      La Jolla, USA
    • Year and Date
      2009-08-28
  • [Remarks] Kobayashi K, Saheki T, Song YZ. Citrin deficiency. In : Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. SourceGeneReviews^<TM>[Internet]. Seattle(WA): University of Washington, Seattle ; 1993-. 2005 Sep 16[updated 2012 Jan 05]

    • URL

      http://www.ncbi.nlm.nih.gov/books/NBK1181/

  • [Patent(Industrial Property Rights)] 成人発症II型シトルリン血症の診断方法2012

    • Inventor(s)
      小林圭子、佐伯武頼、ステファンWシェーラー
    • Industrial Property Rights Holder
      小林圭子、佐伯武頼
    • Industrial Property Number
      特許、特許第4480199号
    • Acquisition Date
      2012-06-08

URL: 

Published: 2013-07-31  

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