Induced FasR Activation and Macrophage Apoptosis in Mice
The iDimerize Inducible Homodimerization technology is used to rewire the Fas-dependent apoptosis pathway, and generate transgenic mice capable of conditional macrophage ablation. Authors show that induced Fas receptor (FasR) oligomerization leads to systemic macrophage apoptosis. Paper: Burnett et al. (2003) J. Leukocyte Biol. 75(23):612–23.
Advantages of inducible dimerization
- Induction is systemic and reversible
- Induce at any developmental stage
- Remove ligand to study phenotype reversibility
Mafia (Macrophage Fas-induced apoptosis) mice with transgenes under the control of a macrophage-specific promoter were created. The cytoplasmic region of FasR, which mediates DISC assembly, was fused with two copies of the DmrB domain and a membrane-targeting domain. FasR oligomerization was induced by intraperitoneal injections with B/B Homodimerizer ligand.*
Mafia mice receiving injections of ligand showed 70–95% loss of macrophages cells, following the 5th day of treatment.
Studies are presented using iDimerize components. For complete experimental details please refer to the original publication. The optimal position and copy number of fusion domains varies per study and must be determined experimentally.