Related Experiment Video

Updated: Feb 6, 2026

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
08:27

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome

Published on: May 22, 2019

6.8K

Analyzing Necroptosis Using an RIPK1 Kinase Inactive Mouse Model of TNF Shock

Matija Zelic1, Michelle A Kelliher2

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.

Methods in Molecular Biology (Clifton, N.J.)
|August 24, 2018
PubMed

Insights

This study investigates the role of RIPK1 kinase activity in necroptosis using novel RIPK1 kinase-inactive mice. Researchers analyzed necroptosis induction in macrophages and a mouse model of TNF-induced shock.

Area of Science:

  • Cellular signaling
  • Immunology
  • Molecular biology

Background:

  • The serine/threonine kinase RIPK1 is a key mediator of cell death pathways, including apoptosis and necroptosis.
  • RIPK1 signaling is implicated in various diseases such as inflammatory bowel disease and ischemia-reperfusion injury.
  • Understanding RIPK1's role in necroptosis is crucial for developing targeted therapies.

Purpose of the Study:

  • To genetically interrogate the role of RIPK1 kinase-mediated necroptosis in disease models.
  • To establish and utilize RIPK1 kinase-inactive mice (Ripk1D138N/D138N) for studying necroptosis.
  • To analyze necroptosis induction in vitro and in vivo.

Main Methods:

  • Utilized kinase-inactive Ripk1D138N/D138N mice.
  • Performed in vitro experiments using bone-marrow derived macrophages (BMDMs).
  • Conducted in vivo studies using a murine model of TNF-induced shock.

Main Results:

  • Demonstrated the ability to analyze necroptosis induction in BMDMs from kinase-inactive mice.
  • Successfully modeled TNF-induced shock in vivo to study RIPK1-dependent necroptosis.
  • Provided a framework for genetically dissecting RIPK1's role in necroptosis.

Conclusions:

  • Kinase-inactive Ripk1D138N/D138N mice are a valuable tool for studying RIPK1-mediated necroptosis.
  • The methodologies described allow for robust in vitro and in vivo analysis of necroptosis.
  • This research facilitates further investigation into RIPK1's pathological roles.
Keywords:
Bone marrow-derived macrophagesCaspase inhibitorCell deathLipopolysaccharideNecroptosisTNF shock

More Related Videos

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

11.3K
Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method16:07

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method

Published on: September 16, 2017

9.7K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.5K
Shock Waves01:16

Shock Waves

While deriving the Doppler formula for the observed frequency of a sound wave, it is assumed that the speed of sound in the medium is greater than the source's speed through it. When this condition is breached, a shock wave occurs.
When the source's speed approaches the speed of sound, constructive interference between successive wavefronts emitted by the source occurs immediately behind it. Initially, scientists believed that this constructive interference would result in such high...
2.6K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
18.8K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
563
Blood Pressure Imbalances and Circulatory Shock01:24

Blood Pressure Imbalances and Circulatory Shock

Disorders affecting blood volume, vascular tone, or vascular function can disrupt vascular homeostasis, including conditions like hypertension, hemorrhage, and shock.
Blood Pressure: Hypertension and Hypotension
Normal blood pressure is 120/80 mm Hg. Elevated blood pressure is 120-129/under 80 mm Hg. Hypertension, warranting treatment at 130/80 mm Hg, is often asymptomatic and can lead to severe cardiovascular events, aneurysms, peripheral arterial disease, chronic renal disease, or cardiac...
1.7K