Impaired myelopoiesis in mice lacking the repressors of translation initiation, 4E-BP1 and 4E-BP2.
We investigated the role of two repressors of translation initiation in granulocytic differentiation using mice with a null mutation in the 4E-BP1 gene or with a null mutation in the 4E-BP2 gene. We show that 4E-BP1(-/-) and 4E-BP2(-/-) mice exhibit an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements compared with wild-type mice, which is suggestive of an impaired granulocytic differentiation. Clonogenetic analyses revealed a reduced number of granulocytic colonies and concomitant increase in granulo-monocytic colonies in 4E-BP(-/-) mice. Finally, a slight expansion of monocytic cells was observed in the 4E-BP2(-/-) mice. In contrast, we did not observe any significant difference in thymocyte maturation in these mice. These results, together with the fact that 4E-BPs are markedly induced during granulo-monocytic differentiation of myeloid cells in vitro, highlight the pivotal role of 4E-BP1 and 4E-BP2 in the early phases of myelopoiesis. These results represent the first in vivo evidence of the involvement of translation in the early phases of granulo-monocytic differentiation and further extend the role of translation in haematopoietic differentiation.
Olson
Katie E
KE
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Booth
Garrett C
GC
Poulin
Francis
F
Sonenberg
Nahum
N
Beretta
Laura
L
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000276:immunology*; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D038042:Myelopoiesis / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; C491255:Eif4ebp2 protein, mouse; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins