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Updated: May 9, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis

Jianfeng Wu1, Zhe Huang, Junming Ren

  • 1State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.

Cell Research
|July 10, 2013
PubMed

Insights

Mixed lineage kinase domain-like protein (Mlkl) is essential for necroptosis but not normal development or immune responses. Mlkl-deficient mice are protected from necrosis-related diseases, confirming Mlkl

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Mixed lineage kinase domain-like protein (Mlkl) interacts with RIP3 and is crucial for TNF-induced necroptosis in cell lines.
  • The in vivo role of Mlkl in necroptosis and its impact on physiological processes remain largely uncharacterized.

Purpose of the Study:

  • To generate and characterize Mlkl-deficient mice to investigate the in vivo function of Mlkl in necroptosis and development.
  • To determine the role of Mlkl in immune cell development and inflammatory signaling pathways.

Main Methods:

  • Generation of Mlkl-deficient mice using TALENs-mediated gene disruption.
  • Assessment of necroptosis and apoptosis resistance in Mlkl-deficient mouse embryonic fibroblasts (MEFs) and macrophages.
  • Analysis of inflammatory signaling pathways (NF-κB, ERK, JNK, p38) and cytokine production (IL-1β, IL-6, TNF) in response to TNF and LPS.
  • Evaluation of disease models including cerulean-induced acute pancreatitis and polymicrobial septic shock.

Main Results:

  • Mlkl-deficient mice exhibit normal development and immune cell populations.
  • Mlkl-deficient MEFs and macrophages are resistant to necrotic stimuli but not apoptotic stimuli.
  • Mlkl deficiency does not affect NF-κB, ERK, JNK, or p38 activation or cytokine production following TNF or LPS stimulation.
  • Mlkl-deficient mice are protected from cerulean-induced acute pancreatitis but not polymicrobial septic shock.

Conclusions:

  • Mlkl is dispensable for normal mouse development and immune cell homeostasis.
  • Mlkl plays a critical role in necroptosis, as evidenced by resistance to necrotic stimuli and protection from pancreatitis.
  • The role of Mlkl in necroptosis is context-dependent, as it does not influence septic shock mortality.

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