Figure 1.
Loss of 1 copy of Ctnnb1 is sufficient to prevent fatal macrocytic anemia in Apcdel/+ mice. (A) Kaplan-Meier survival curves for Apcdel/+ (A; n = 34), Apcdel/+, Ctnnb1del/+ (AC; n = 11), Ctnnb1del/+ (C; n = 6), and Apcfl/+, Ctnnb1fl/+ (Cre−; n = 8) control mice. The median survival of Apcdel/+ mice was 255 days (previously published by Stoddart et al20 ); thus, the A and AC mice were not littermates in this figure. All other mouse cohorts, monitored monthly for the development of macrocytic anemia, survived until the end of the study (∼400 days) (B) RBC parameters from complete blood counts (CBCs) and spleen size. CBCs and spleen size for Apcdel/+ mice were measured at the time of sacrifice, and for the other 3 cohorts were measured at the end of the study (∼400 days). Circles represent 2 Apcdel/+, Ctnnb1del/+ mice that displayed moderate anemia and splenomegaly at the end of the study, suggestive of the onset of MDS. (C) Representative flow cytometric analysis of erythroid (CD71+Ter119+) and B cells (CD19+IgM+) in spleen isolated from mice for each cohort. Shown is the average percentage of CD71+Ter119+ erythroblasts and CD19loIgM+ (immature) and CD19hiIgM+ (mature) B cells from at least 3 mice from each cohort. In contrast to Apcdel/+ mice, 9 of 11 Apcdel/+, Ctnnb1del/+ mice (82%) had a normal distribution of erythroid cells and B cells in the spleen, similar to controls. Analysis of the 2 exceptional Apcdel/+, Ctnnb1del/+ mice with splenomegaly and moderate anemia is shown in supplemental Table 2. MCV, mean corpuscular volume.