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Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis

Open access
Wu, Jianfeng, Huang, Zhe, Ren, Junming, Zhang, Zhirong, He, Peng, Li, Yangxin, Ma, Jianhui, Chen, Wanze, Zhang, Yingying, Zhou, Xiaojuan, Yang, Zhentao, Wu, Su-Qin, Chen, Lanfen, Han, Jiahuai·2013·Cell Research

Abstract

Mixed lineage kinase domain-like protein (Mlkl) was recently found to interact with receptor interacting protein 3 (Rip3) and to be essential for tumor necrosis factor (TNF)-induced programmed necrosis (necroptosis) in cultured cell lines. We have generated Mlkl-deficient mice by transcription activator-like effector nucleases (TALENs)-mediated gene disruption and found Mlkl to be dispensable for normal mouse development as well as immune cell development. Mlkl-deficient mouse embryonic fibroblasts (MEFs) and macrophages both showed resistance to necrotic but not apoptotic stimuli. Mlkl-deficient MEFs and macrophages were indistinguishable from wild-type cells in their ability to activate NF-κB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides (LPS), respectively. Consistently, Mlkl-deficient macrophages and mice exhibited normal interleukin-1β (IL-1β), IL-6, and TNF production after LPS treatment. Mlkl deficiency protects mice from cerulean-induced acute pancreatitis, a necrosis-related disease, but has no effect on polymicrobial septic shock-induced animal death. Our results provide genetic evidence for the role of Mlkl in necroptosis.

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Research works printed but not linked: 33

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Metadata

Authors
Wu, J., Huang, Z., Ren, J., Zhang, Z., He, P., Li, Y., Ma, J., Chen, W., Zhang, Y., Zhou, X., Yang, Z., Wu, S.-Q., Chen, L., & Han, J.
Venue
Cell Research
Published
2013-07-09
Volume
23
Issue
8
Pages
994-1006
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
OpenAlex
W2124396497
Cited by
462
References
14
FWCI
19.90
Type
journal article
Language
en
Open access
hybrid
Licence
creativecommons.org/licenses/by-nc-nd/3.0 (tdm)

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CoChat. (2026). Citation check: Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. https://app.cochat.ai/papers/10.1038/cr.2013.91
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Wu, J., Huang, Z., Ren, J., Zhang, Z., He, P., Li, Y., Ma, J., Chen, W., Zhang, Y., Zhou, X., Yang, Z., Wu, S.-Q., Chen, L., & Han, J. (2013). Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Research. https://doi.org/10.1038/cr.2013.91

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