Brief report Reassessment of interactions between hematopoietic receptors using common beta-chain and interleukin-3–specific receptor beta-chain–null cells: no evidence of functional interactions with receptors for erythropoietin, granulocyte colony-stimulating factor, or stem cell factor

Mice lacking both the gene encoding the shared receptor for granulocyte macrophage–colony-stimulating factor (GMCSF), interleukin-3 (IL-3), and IL-5 common b-chain (Bc) and the gene for the IL-3 specific receptor (BIL3) were generated. This was achieved by targeting the Bc locus in embryonic stem cells that were heterozygous for a null mutation of BIL3. Cells from mice generated with the doubly targeted embryonic stem cells were unresponsive to all 3 cytokines. Considerable previous data suggested a role for common beta-chain (bc) in modulating signaling of cytokines including erythropoietin (EPO), G-CSF, and stem cell factor (SCF). However, bone marrow cells from mice lacking bc and bIL3 showed normal responsiveness to these cytokines. Thus, there was no evidence for a biologically significant interaction between signaling via bc or bIL3 and signaling by EPO, GCSF, or SCF. Previously documented biochemical phenomena, including receptor transmodulation, receptor transphosphorylation, and even direct physical interaction, involving the bc/bIL-3 receptor systems do not reflect genuine interactions of physiological significance in primary hematopoietic cells. This study provided results that challenge conclusions previously established using a variety of biochemicalassays. (Blood.2000;96:1588-1590)