Published online 11 February 2009
Haematologica, Vol 94, Issue 3, 326-334 doi:10.3324/haematol.13635
Copyright © 2009 by Ferrata Storti Foundation
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Original Article

TAM receptors and the regulation of erythropoiesis in mice

Hongmei Tang1, Song Chen1, Haikun Wang1, Hui Wu1, Qingxian Lu2, Daishu Han1

1 Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing;
2 Department of Ophthalmology, School of Medicine, Capital Medical University, Beijing, China

Correspondence: Daishu Han, Ph.D, Department of Cell Biology, PUMC & CAMS 5 Dong Dan San Tiao, Beijing 100005, P.R. China. E-mail:daishu{at}public.bta.net.cn

Background: TAM receptors (Tyro3, Axl and Mer) are expressed in hematopoietic tissues. The roles of the three receptors in hematopoiesis are, however, largely unknown. We investigated the role of TAM receptors in regulating erythropoiesis.

Design and Methods: Single and double mutant mice for Axl and Mer were used in the study. Cellularity of bone marrow and spleen, hematologic parameters, flow cytometry analysis of erythroid cell maturation, erythropoietic response to acute hemolytic anemia, bone marrow transplantation and the expression of erythropoisis were analyzed to evaluate the function of Axl and Mer in erythropoiesis.

Results: Axl and Mer, but not Tyro3, were constitutively expressed in developing erythroid cells. Mice lacking Axl and Mer (Axl–/–Me–/–) had impaired erythropoiesis in bone marrow and expanded splenic erythropoiesis. We found an inhibition of differentiation at the transition from erythroid progenitors to proerythroblasts in Axl–/–Mer–/– mice. These mice exhibited a low rate of erythropoietic response to acute anemia induced by phenylhydrazine. Bone marrow transplantation studies showed that the impaired erythropoiesis in Axl–/–Mer–/– mice is erythroid cell-autonomous. TAM receptors may influence erythropoiesis through the regulation of GATA-1 erythropoietin receptor and EpoR expression in erythroid progenitors. Notably, mice lacking single Axl or Mer exhibited normal erythropoiesis in steady-state conditions.

Conclusions: Axl and Mer play an important role in regulating erythropoiesis. This finding provides a novel insight into the mechanism of erythropoiesis.

Key words: Axl, Mer, erythropoiesis, hematopoiesis.




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Y. Chen, H. Wang, N. Qi, H. Wu, W. Xiong, J. Ma, Q. Lu, and D. Han
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