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Veterinary Research Communications

, Volume 42, Issue 1, pp 49–56 | Cite as

R132 mutations in canine isocitrate dehydrogenase 1 (IDH1) lead to functional changes

  • Shota Kawakami
  • Kazuhiko OchiaiEmail author
  • Daigo Azakami
  • Yuiko Kato
  • Masaki Michishita
  • Masami Morimatsu
  • Toshina Ishiguro-Oonuma
  • Eri Onozawa
  • Masami Watanabe
  • Toshinori Omi
Original Article

Abstract

Glioma is the second most common intracranial neoplasia in dogs, but the pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 1 (IDH1) is frequently mutated in gliomas. Although almost all human IDH1 mutations have been identified as involving the Arg132 codon, few studies have reported structural, functional, and mutational information for canine IDH1. Therefore, in this study, we cloned the canine IDH1 homologue and used PCR mutagenesis to substitute the wildtype (WT) Arg132 with His (R132H) or Ser (R132S). WT and mutated IDH1 were overexpressed in HeLa cells, and their presence was confirmed by immunoblotting and immunocytochemistry using mutation-specific antibodies. The IDH1 activity between WT, R132H, and R132S transfectants was compared by measuring the production of NADH and NADPH. NADPH production in R132H and R132S transfectants was lower than that in WT, but NADH levels were not significantly different. Finally, we detected increased expression of hypoxia inducible factor 1 alpha (HIF-1α) in the R132H and R132S transfectants. These results indicated that the canine IDH1 Arg132 mutation has the potential to induce carcinogenesis in canine somatic cells.

Keywords

Canine Glioma Isocitrate dehydrogenase 1 Mutation 

Notes

Acknowledgements

This work was supported by KAKENHI scientific research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 15K07754).

Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

Informed consent

This manuscript does not contain any studies with human subjects performed by any of the authors.

Human and animal rights

All experiments were executed according to the Guide for the Care and Use of Laboratory Animals and approved by the institutional animal ethics committee.

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  • Shota Kawakami
    • 1
  • Kazuhiko Ochiai
    • 1
    Email author
  • Daigo Azakami
    • 1
  • Yuiko Kato
    • 1
  • Masaki Michishita
    • 2
  • Masami Morimatsu
    • 3
  • Toshina Ishiguro-Oonuma
    • 4
  • Eri Onozawa
    • 1
  • Masami Watanabe
    • 5
  • Toshinori Omi
    • 1
  1. 1.School of Veterinary Nursing and Technology, Faculty of Veterinary ScienceNippon Veterinary and Life Science UniversityTokyoJapan
  2. 2.Department of Veterinary Pathology, Faculty of Veterinary ScienceNippon Veterinary and Life Science UniversityTokyoJapan
  3. 3.Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary MedicineHokkaido UniversitySapporoJapan
  4. 4.Laboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of AgricultureIwate UniversityMoriokaJapan
  5. 5.Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan

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