Generation of a new FcRγ^fl/fl mouse. A new mouse was designed to have conditional expression of activating Fc receptors. (A) Fcer1g gene locus showing insertion of LoxP recognition sequences flanking exons 2 and 3. Splenocytes were harvested from B6, FcRγ^fl/fl, FcRγ^fl/fl × CMV^Cre+, and Fcer1g^−/− mice and (B) evaluated for expression of FcγRI, FcγRIII, FcγRIV, and FcγRIIb on multiple leukocyte subsets; MFIs of FcγRs are displayed in a heat map. To evaluate whether insertion of LoxP sites interfered with clearance and alloantibody production, B6 and FcRγ^fl/fl mice were passively immunized with anti-HOD mAb followed by an RBC transfusion. HOD RBC survival (C) and anti-HOD alloantibodies (D) were evaluated over 21 days. In analogous experiments, immune responses in FcRγ^fl/fl × CMV^Cre+, and Fcer1g^−/− were directly compared and HOD RBC survival (E) and anti-HOD alloantibody production (F) were evaluated. Each experiment was performed 3 times with 3 to 5 mice per group. Representative data are shown. Data were analyzed with a repeated measures 2-way ANOVA with multiple comparisons test to control B6 mice. ****P ≤ .0001.