TAM receptors and the regulation of erythropoiesis in mice.
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.


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.
Tang
Hongmei
H
Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, P.R. China.
Chen
Song
S
Wang
Haikun
H
Wu
Hui
H
Lu
Qingxian
Q
Han
Daishu
D
D000208:Acute Disease; D000743:Anemia, Hemolytic / Q000097:blood; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase
D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse