Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors

Effects of human γ‐globin in murine β‐thalassaemia

“…This animal had a total Hb level of 11AE5 g/dl and haematocrit of 37%. This level of anaemia is compatible with survival in mice, and is equivalent to the haematological phenotype of W/W v mice (Antonchuck et al, 2004). However, even this animal failed to survive past 2 months of age.…”

Incomplete restoration of Mpl expression in the mpl−/− mouse produces partial correction of the stem cell–repopulating defect and paradoxical thrombocytosis

“…As expected, the repopulating ability of the mpl Ϫ/Ϫ marrow was severely impaired at only 3.6% plus or minus 0.8% of WT marrow (Figure 3). [5][6][7][8] In comparison, the Tg(mpl) mice demonstrated a nearly 10-fold increase in marrow-repopulating activity, though the recovery was still not complete, reaching 33.5% plus or minus 5.6% of the WT Ly5.1 level. Thus, the transgenic vector used to restore mpl expression in the mpl Ϫ/Ϫ mouse generates overcorrection of the platelet count but incomplete recovery of stem cell-repopulating activity.…”

“…2 Both TPO-deficient (Tpo Ϫ/Ϫ ) and Mpl-deficient (mpl Ϫ/Ϫ ) mice exhibit severe thrombocytopenia, 3,4 and marrow cells transplanted from mpl Ϫ/Ϫ mice demonstrate a profound repopulating defect. [5][6][7][8] In humans, loss-offunction mutations in Mpl are the cause for the clinical disorder congenital amegakaryocytic thrombocytopenia (CAMT). 9,10 Individuals with CAMT present with isolated thrombocytopenia in early childhood and eventually develop marrow failure with pancytopenia.…”

Erythropoiesis and globin switching in compound Klf1::Bcl11a mutant mice

“…Reticulocyte counts are higher in young mice and stabilize after 6 weeks of age. 32 We therefore included only the analysis of CD71 expression in mice .10 weeks old as marker for reticulocytes and of Ter119 as a marker for all erythroid cells (Figure 2A). We found increased CD71 expression in all mutant animals.…”