| First Author | Zhao Q | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 4 | Pages | 798-808 |
| PubMed ID | 28445730 | Mgi Jnum | J:254599 |
| Mgi Id | MGI:6103826 | Doi | 10.1016/j.celrep.2017.04.011 |
| Citation | Zhao Q, et al. (2017) RIPK3 Mediates Necroptosis during Embryonic Development and Postnatal Inflammation in Fadd-Deficient Mice. Cell Rep 19(4):798-808 |
| abstractText | RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase domain (Ripk3(Delta/Delta) mice), thus abolishing its kinase activity. Ripk3(Delta/Delta) cells were resistant to necroptosis stimulation in vitro, and Ripk3(Delta/Delta) mice were protected from necroptotic diseases. Although the Ripk3(Delta/Delta) mutation rescued embryonic lethality in Fadd(-/-) embryos, Fadd(-/-)Ripk3(Delta/Delta) mice died within 1 day after birth due to massive inflammation. These results indicate that Ripk3 ablation rescues embryonic lethality in Fadd-deficient mice by suppressing two RIPK3-mediating processes: necroptosis during embryogenesis and inflammation during postnatal development in Fadd(-/-) mice. |
