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The Journal of Physiological Sciences

, Volume 69, Issue 1, pp 103–112 | Cite as

Characterization of Δ(G970-T1122)-CFTR, the most frequent CFTR mutant identified in Japanese cystic fibrosis patients

  • Kanako Wakabayashi-Nakao
  • Yingchun Yu
  • Miyuki Nakakuki
  • Tzyh-Chang Hwang
  • Hiroshi Ishiguro
  • Yoshiro SohmaEmail author
Original Paper

Abstract

A massive deletion over three exons 16-17b in the CFTR gene was identified in Japanese CF patients with the highest frequency (about 70% of Japanese CF patients definitely diagnosed). This pathogenic mutation results in a deletion of 153 amino acids from glycine at position 970 (G970) to threonine at 1122 (T1122) in the CFTR protein without a frameshift. We name it Δ(G970-T1122)-CFTR. In the present study, we characterized the Δ(G970-T1122)-CFTR expressed in CHO cells using immunoblots and a super resolution microscopy. Δ(G970-T1122)-CFTR proteins were synthesized and core-glycosylated but not complex-glycosylated. This observation suggests that the Δ(G970-T1122) mutation can be categorized into the class II mutation like ΔF508. However, VX-809 a CFTR corrector that can help maturation of ΔF508, had no effect on Δ(G970-T1122). Interestingly C-terminal FLAG tag seems to partially rescue the trafficking defect of Δ(G970-T1122)-CFTR; however the rescued Δ(G970-T1122)-CFTR proteins do not assume channel function. Japanese, and perhaps people in other Asian nations, carry a class II mutation Δ(G970-T1122) with a higher frequency than previously appreciated. Further study of the Δ(G970-T1122)-CFTR is essential for understanding CF and CFTR-related diseases particularly in Asian countries.

Keywords

Cystic fibrosis CFTR Mutation Japanese Asian 

Notes

Acknowledgements

We are grateful to Drs. Yoichiro Abe and Masato Yasui (Keio University) for their useful help and discussions. We are also grateful to the Collaborative Research Resources, Keio University School of Medicine for equipment and technical supports. K.W.-N. is a Japan Society for the Promotion of Sciences (JSPS) Research Fellow. This work was supported by JSPS KAKENHI Grant Numbers 17J40033 (K.W.-N.), 25293049, 15K15035, 16H05122 (Y.S.), and 16K09392 (H.I.).

Author contributions

KW-N designed and performed the molecular biological and biochemical experiments and helped write the manuscript. Y-CY designed and performed the electro-physiological experiments and helped write the manuscript. MN designed the molecular biological experiments and T-CH designed the electro-physiological experiments. HI conceptualized the project and helped write the manuscript. YS conceptualized the project, designed the experiments, and helped write the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences and Center for Medical SciencesInternational University of Health and WelfareOtawaraJapan
  2. 2.Dalton Cardiovascular Research CenterUniversity of MissouriColumbiaUSA
  3. 3.Department of Medical Pharmacology and PhysiologyUniversity of MissouriColumbiaUSA
  4. 4.Department of Human NutritionNagoya University Graduate School of MedicineNagoyaJapan
  5. 5.Department of PharmacologyKeio University School of MedicineTokyoJapan

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