Figure 3.
Rpl11 haploinsufficient chimeras model DBA mosaicism. (A) The experimental design for generation of 0%, 50%, 80%, and 100% mutant chimeras and their controls. Flvcr1-deleted (FFMx) and Mxcre (++Mx) control mice are treated with pIpC, whereas Rpl11 haploinsufficient (+LT2) and T2cre (++T2) control mice are treated with tamoxifen starting 5 weeks before transplant. Marrow cells from femurs and tibias from the deleted and control mice were mixed with wild-type marrow cells from untreated ubiquitin-GFP mice (WT GFP) at 50:50 and 80:20 ratios and then transplanted into recipient mice. Because mice receiving 100% Flvcr1-deleted marrow succumb to severe anemia by 7 weeks posttransplant,13 the 100% FFMx and control ++Mx transplants were performed before pIpC treatment. These recipient mice were then treated with pIpC after engraftment 4 weeks later. Deletion efficiency of donor mice is shown in supplemental Figure 1. (B) Monthly analysis of red cell counts and MCV of Rpl11 chimeras, Flvcr chimeras, along with their respective cre control chimeras. (C) The relative RBC, Hb, and HCT of Rpl11 and Flvcr chimeras compared with transplants that received 100% deleted (0% recovery) or control (100% recovery) marrow. MCV is presented as a percent of control transplants. (D) The frequency of peripheral blood granulocytes, RBC, B cells, and T cells that were from the WT (GFP+) partner cells in the chimeric mice 16 weeks after transplant are shown with significant differences compared with the respective control chimeras indicated. Data are presented as mean ± standard deviation (mean ± standard error of the mean, panel C) from 3 to 8 Flvcr chimeras, 6 Mx control chimeras, 6 to 9 Rpl11 chimeras, and 7 T2 control chimeras. *P < .05; **P < .01; ***P < .001 from Student t test. CBC, complete blood count; ctrl, control; Hb, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; pIpC, polyI-polyC.