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

Research output: Contribution to journalArticle

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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 languageEnglish
Article number12765
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

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Clustered Regularly Interspaced Short Palindromic Repeats
Natural Killer T-Cells
Metabolic Diseases
T-Cell Antigen Receptor
Technology
Embryonic Stem Cells
Cell Biology
Insulin Resistance
Immune System
Obesity
Genes

ASJC Scopus subject areas

  • General

Cite this

A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease. / Ren, Yue; Sekine-Kondo, Etsuko; Shibata, Risa; Kato-Itoh, Megumi; Umino, Ayumi; Yanagida, Ayaka; Satoh, Masashi; Inoue, Komaki; Yamaguchi, Tomoyuki; Mochida, Keiichi; Nakae, Susumu; Van Kaer, Luc; Iwabuchi, Kazuya; Nakauchi, Hiromitsu; Watarai, Hiroshi.

In: Scientific Reports, Vol. 7, No. 1, 12765, 01.12.2017.

Research output: Contribution to journalArticle

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
Ren, Yue ; Sekine-Kondo, Etsuko ; Shibata, Risa ; Kato-Itoh, Megumi ; Umino, Ayumi ; Yanagida, Ayaka ; Satoh, Masashi ; Inoue, Komaki ; Yamaguchi, Tomoyuki ; Mochida, Keiichi ; Nakae, Susumu ; Van Kaer, Luc ; Iwabuchi, Kazuya ; Nakauchi, Hiromitsu ; Watarai, Hiroshi. / A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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