Cl. Semerad et al., A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation, IMMUNITY, 11(2), 1999, pp. 153-161
To investigate the specificity of cytokine signals in hematopoietic differe
ntiation, we generated mice with a targeted mutation of their G-CSF recepto
r (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is re
placed with the cytoplasmic domain of the erythropoietin receptor. In homoz
ygous mutant mice, expression of this chimeric receptor had no apparent aff
ect on lineage commitment and was able to support the production of morphol
ogically mature neutrophils. However, mutant neutrophils displayed reduced
chemotaxis, and G-CSF-stimulated mobilization of neutrophils and hematopoie
tic progenitors from the bone marrow to blood was markedly impaired. Thus,
the G-CSFR is generating unique signals that are required for certain speci
alized hematopoietic cell functions but are not required for granulocytic d
ifferentiation or lineage commitment.