| First Author | Wu J | Year | 2013 |
| Journal | Cell Res | Volume | 23 |
| Issue | 8 | Pages | 994-1006 |
| PubMed ID | 23835476 | Mgi Jnum | J:204622 |
| Mgi Id | MGI:5532894 | Doi | 10.1038/cr.2013.91 |
| Citation | Wu J, et al. (2013) Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res 23(8):994-1006 |
| abstractText | 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-kappaB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides (LPS), respectively. Consistently, Mlkl-deficient macrophages and mice exhibited normal interleukin-1beta (IL-1beta), 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. |
