Using iDimerize Inducible Protein Dimerization In Vivo
Many of the in vitro applications for chemical induced dimerization (CID) have progressed into transgenic animals. The B/B Homodimerizer (AP20187) has been the most widely used in vivo, and typically investigators have used doses of 0.5–10 mg per kg for each injection. At this dosage, 5 mg of dimerizer is sufficient for 20–400 injections for a 25 g mouse. However, the exact dose and treatment must be determined empirically for each experiment.
Examples of In Vivo Mouse Models for Disease
The MaFIA mouse model
Macrophages are believed to play an important role in tumor development and progression. The Macrophage Fas-Induced Apoptosis (MaFIA) mouse is a widely adopted mouse model that allows for selective removal of macrophages through apoptosis (1). The mechanism involves expression of a fas-DmrB fusion protein from a myeloid-specific promoter and its induced trimerization with the B/B Homodimerizer (AP20187). Trimerization of the fas death domain activates the caspase 8 pathway and leads to macrophage ablation in MaFIA mice (see Data & Images tab).
Studying the roles of FGF receptor subtypes in prostate cancer
Prostate-specific expression of inducible versions of two subtypes of fibroblast growth factor receptor, FGFR-1 and FGFR-2, showed that only FGFR-1 induced neoplasia/hyperplasia in the prostate—implying its role for early prostate cancer development (2; see Data & Images tab). This mouse model can be used to test drug candidates that block the effects of FGFR1 dimerization.