A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

Yue Ren; Etsuko Sekine-Kondo; Risa Shibata; Megumi Kato-Itoh; Ayumi Umino; Ayaka Yanagida; Masashi Satoh; Komaki Inoue; Tomoyuki Yamaguchi; Keiichi Mochida; Susumu Nakae; Luc Van Kaer; Kazuya Iwabuchi; Hiromitsu Nakauchi; Hiroshi Watarai

doi:10.1038/s41598-017-12475-4

A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

Yue Ren, Etsuko Sekine-Kondo, Risa Shibata, Megumi Kato-Itoh, Ayumi Umino, Ayaka Yanagida, Masashi Satoh, Komaki Inoue, Tomoyuki Yamaguchi, Keiichi Mochida, Susumu Nakae, Luc Van Kaer, Kazuya Iwabuchi, Hiromitsu Nakauchi, Hiroshi Watarai

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Abstract

iNKT cells play important roles in immune regulation by bridging the innate and acquired immune systems. The functions of iNKT cells have been investigated in mice lacking the Traj18 gene segment that were generated by traditional embryonic stem cell technology, but these animals contain a biased T cell receptor (TCR) repertoire that might affect immune responses. To circumvent this confounding factor, we have generated a new strain of iNKT cell-deficient mice by deleting the Traj18 locus using CRISPR/Cas9 technology, and these animals contain an unbiased TCR repertoire. We employed these mice to investigate the contribution of iNKT cells to metabolic disease and found a pathogenic role of these cells in obesity-associated insulin-resistance. The new Traj18-deficient mouse strain will assist in studies of iNKT cell biology.

Original language	English
Article number	12765
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-12475-4
Publication status	Published - Dec 1 2017

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Ren, Y., Sekine-Kondo, E., Shibata, R., Kato-Itoh, M., Umino, A., Yanagida, A., Satoh, M., Inoue, K., Yamaguchi, T., Mochida, K., Nakae, S., Van Kaer, L., Iwabuchi, K., Nakauchi, H., & Watarai, H. (2017). A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease. Scientific reports, 7(1), [12765]. https://doi.org/10.1038/s41598-017-12475-4

Ren, Y, Sekine-Kondo, E, Shibata, R, Kato-Itoh, M, Umino, A, Yanagida, A, Satoh, M, Inoue, K, Yamaguchi, T, Mochida, K, Nakae, S, Van Kaer, L, Iwabuchi, K, Nakauchi, H & Watarai, H 2017, 'A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease', Scientific reports, vol. 7, no. 1, 12765. https://doi.org/10.1038/s41598-017-12475-4

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abstract = "iNKT cells play important roles in immune regulation by bridging the innate and acquired immune systems. The functions of iNKT cells have been investigated in mice lacking the Traj18 gene segment that were generated by traditional embryonic stem cell technology, but these animals contain a biased T cell receptor (TCR) repertoire that might affect immune responses. To circumvent this confounding factor, we have generated a new strain of iNKT cell-deficient mice by deleting the Traj18 locus using CRISPR/Cas9 technology, and these animals contain an unbiased TCR repertoire. We employed these mice to investigate the contribution of iNKT cells to metabolic disease and found a pathogenic role of these cells in obesity-associated insulin-resistance. The new Traj18-deficient mouse strain will assist in studies of iNKT cell biology.",

author = "Yue Ren and Etsuko Sekine-Kondo and Risa Shibata and Megumi Kato-Itoh and Ayumi Umino and Ayaka Yanagida and Masashi Satoh and Komaki Inoue and Tomoyuki Yamaguchi and Keiichi Mochida and Susumu Nakae and {Van Kaer}, Luc and Kazuya Iwabuchi and Hiromitsu Nakauchi and Hiroshi Watarai",

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AU - Kato-Itoh, Megumi

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A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

Abstract

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