Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs

Elena Yukie Yoshitoshi-Uebayashi, Taro Toyoda, Katsutaro Yasuda, Maki Kotaka, Keiko Nomoto, Keisuke Okita, Kentaro Yasuchika, Shinya Okamoto, Noriyuki Takubo, Toshiya Nishikubo, Tomoyoshi Soga, Shinji Uemoto, Kenji Osafune

Research output: Contribution to journalArticle

7 Citations (Scopus)


Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns. Therapeutic options are limited, and neurological sequelae may persist. To understand the pathophysiology and find novel treatments, induced pluripotent stem cells (iPSCs) were generated from a CTLN1 patient and differentiated into hepatocyte-like cells (HLCs). CTLN1-HLCs have lower ureagenesis, recapitulating part of the patient's phenotype. L-arginine, an amino acid clinically used for UCD treatment, improved this phenotype in vitro. Metabolome analysis revealed an increase in tricarboxylic acid (TCA) cycle metabolites in CTLN1, suggesting a connection between CTLN1 and the TCA cycle. This CTLN1-iPSC model improves the understanding of CTLN1 pathophysiology and can be used to pursue new therapeutic approaches.

Original languageEnglish
Pages (from-to)613-619
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2017 May 6


  • Argininosuccinate synthetase
  • Citrullinemia type 1
  • Hepatocyte
  • iPSC
  • L-arginine
  • Urea cycle disorder

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Yoshitoshi-Uebayashi, E. Y., Toyoda, T., Yasuda, K., Kotaka, M., Nomoto, K., Okita, K., Yasuchika, K., Okamoto, S., Takubo, N., Nishikubo, T., Soga, T., Uemoto, S., & Osafune, K. (2017). Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs. Biochemical and Biophysical Research Communications, 486(3), 613-619.