Conditional deletion of Gdf11 in the entire hematopoietic compartment or pancellularly in thalassemic (Hbb^th3/+) mice does not improve hematological parameters. (A-D) Conditional deletion of Gdf11 in the entire hematopoietic compartment of thalassemic mice (Hbb^th3/+Vav^CreGdf11^Δ2-3/Δ2-3) (n = 9) does not result in any differences in RBC count, Hb, Hct, or reticulocytes compared with Hbb^th3/+ controls (n = 15). (E-H) Conditional deletion of Gdf11 in erythroid cells of nonthalassemic wild-type animals (Hbb^+/+) does not result in altered hematopoietic parameters in Hbb^+/+Vav^CreGdf11^Δ2-3/Δ2-3 mice (n = 23) compared with Hbb^+/+ controls (n = 22). CBCs were analyzed at 2 months of age. Ubiquitous deletion of Gdf11 in Hbb^th3/+Rosa^CreGdf1^flox/flox mice treated with TAM (Hbb^th3/+Rosa^CreGdf11^Δ2-3/Δ2-3) does not improve hematological parameters. (I-L) Hbb^th3/+Rosa^CreGdf11^Δ2-3/Δ2-3 mice (n = 9) did not show increases in RBC, Hb, or Hct or lower reticulocyte counts compared with Hbb^th3/+Gdf11^flox/flox control mice (n = 7). (M-P) No hematological differences were detectable in Hbb^+/+Rosa^CreGdf11^Δ2-3/Δ2-3 mice (n = 17) compared with Hbb^+/+Gdf11^flox/flox controls (n = 15). Rosa^CreGdf11^Δ2-3/Δ2-3 mice and Gdf11^flox/flox controls were analyzed between 3 and 6 months of age. CBCs were analyzed 2 weeks post-TAM administration. Females and males were included in the analysis. (Q) Messenger RNA analysis of Gdf11^Δ2-3/Δ2-3 mice confirms reduction of Gdf11 in spleens. Messenger RNA from Hbb^th3/+Vav^CreGdf11^Δ2-3/Δ2-3 (n = 3) and Hbb^th3/+Rosa^CreGdf11^Δ2-3/Δ2-3 (n = 3) age-matched males (5 months old) was assessed for Gdf11 reduction in the spleen, by qRT-PCR, using a Gdf11 probe specific for exon 2. Both show significant reductions normalized by Hprt (left panel). Gdf8 was undetectable in all samples tested. No statistical differences were found in the Gypa positive control (right panel). Data are mean ± standard deviation. *P ≤ .05, Student t test.