Figure 5.
Calr haploinsufficiency restores the functions of hematopoietic stem cells impaired by the CALRdel52 mutation. (A) Competitive repopulation assay. LSK cells (1 × 103 cells) sorted from WT mice, CALRdel52;Calr+/+ mice, and CALRdel52;Calr+/− mice (B6-CD45.2) together with 1 × 106 WT unpurified BM competitor cells (B6-CD45.1) were transplanted into lethally irradiated recipients (B6-CD45.1). Donor chimerism was calculated as CD45.2/(CD45.1 + CD45.2). (B) The percentage of chimerism of donor cells was recorded for 10 months (n = 14 in each group). (C) BM histopathology and megakaryocyte number. Megakaryocytes in BM were significantly increased in CALRdel52;Calr+/− mice (n = 5) compared with WT (n = 4) and CALRdel52;Calr+/+ (n = 5) mice (bars represent 20 μm). (D) Average complete blood cell counts (n = 14 in each group). (A-B) For comparison of hematologic values over time, ANOVA with repeated measures was used. (C) One-way ANOVA followed by the Tukey-Kramer test was used to assess the number of megakaryocytes among groups. *P < .05; **P < .01; n.s., not significant.

Calr haploinsufficiency restores the functions of hematopoietic stem cells impaired by the CALRdel52 mutation. (A) Competitive repopulation assay. LSK cells (1 × 103 cells) sorted from WT mice, CALRdel52;Calr+/+ mice, and CALRdel52;Calr+/− mice (B6-CD45.2) together with 1 × 106 WT unpurified BM competitor cells (B6-CD45.1) were transplanted into lethally irradiated recipients (B6-CD45.1). Donor chimerism was calculated as CD45.2/(CD45.1 + CD45.2). (B) The percentage of chimerism of donor cells was recorded for 10 months (n = 14 in each group). (C) BM histopathology and megakaryocyte number. Megakaryocytes in BM were significantly increased in CALRdel52;Calr+/− mice (n = 5) compared with WT (n = 4) and CALRdel52;Calr+/+ (n = 5) mice (bars represent 20 μm). (D) Average complete blood cell counts (n = 14 in each group). (A-B) For comparison of hematologic values over time, ANOVA with repeated measures was used. (C) One-way ANOVA followed by the Tukey-Kramer test was used to assess the number of megakaryocytes among groups. *P < .05; **P < .01; n.s., not significant.

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