An inducible model for specific neutrophil depletion by diphtheria toxin in mice

Tianzhu Chao; Liaoxun Lu; Lichen Zhang; Rong Huang; Zhuangzhuang Liu; Binhui Zhou; Eryan Kong; Zhongjian Zhang; Toby Lawrence; Yinming Liang

doi:10.1007/s11427-020-1839-3

An inducible model for specific neutrophil depletion by diphtheria toxin in mice

Sci China Life Sci. 2021 Aug;64(8):1227-1235. doi: 10.1007/s11427-020-1839-3. Epub 2021 Jan 6.

Authors

Tianzhu Chao^#^{1

2}, Liaoxun Lu^#^{1

3

2}, Lichen Zhang^#^{3

2}, Rong Huang^{3

2}, Zhuangzhuang Liu^{1

2}, Binhui Zhou¹, Eryan Kong¹, Zhongjian Zhang¹, Toby Lawrence^{4

5}, Yinming Liang^{6

7

8}

Affiliations

¹ Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, 453003, China.
² Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China.
³ Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China.
⁴ Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China. toby.lawrence@kcl.ac.uk.
⁵ Centre for Inflammation Biology and Cancer Immunology, King's College London, London, SE1 1UL, UK. toby.lawrence@kcl.ac.uk.
⁶ Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, 453003, China. yinming.liang@gris.org.cn.
⁷ Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China. yinming.liang@gris.org.cn.
⁸ Laboratory of Genetic Regulators in the Immune System, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China. yinming.liang@gris.org.cn.

^# Contributed equally.

PMID: 33420927
DOI: 10.1007/s11427-020-1839-3

Abstract

Neutrophils are crucial for immunity and play important roles in inflammatory diseases; however, mouse models selectively deficient in neutrophils are limited, and neutrophil-specific diphtheria toxin (DT)-based depletion system has not yet been established. In this study, we generated a novel knock-in mouse model expressing diphtheria toxin receptor (DTR) under control of the endogenous Ly6G promoter. We showed that DTR expression was restricted to Ly6G⁺ neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h intervals. We characterized the effects of specific neutrophil depletion in mice at steady-state, with acute inflammation and during tumor growth. Our study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.

Keywords: DTR; Ly6G; neutrophil depletion; tumor.

MeSH terms

Animals
Diphtheria Toxin / immunology*
Disease Models, Animal
Heparin-binding EGF-like Growth Factor / immunology*
Mice
Mice, Inbred C57BL
Neoplasms / immunology
Neutrophils / immunology*

Substances

Diphtheria Toxin
Heparin-binding EGF-like Growth Factor