Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | e376-e384 |
Journal | Immunology |
Volume | 128 |
Issue number | 1 PART 2 |
DOIs | |
State | Published - Sep 2009 |
Externally published | Yes |
Keywords
- Granulocytic maturation
- Knockout mice
- Translation initiation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology