Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor beta-chain: implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells.
The receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 and -5 (IL-3, IL-5) share a common signaling subunit (beta c). However, in the mouse, IL-3 can also use an alternative IL-3-specific receptor beta-chain (beta IL-3). To assess the relative contributions of beta c and beta IL-3 to IL-3 receptor formation and function, mice were generated in which the beta IL-3 gene was functionally inactivated by replacement of exons 9-13 with a neomycin resistance cassette. Bone marrow cells from these mice displayed a lower affinity IL-3 receptor than normal and were hyporesponsive to IL-3, but the mice displayed no obvious hematopoietic abnormalities. The data suggested that beta c and beta IL-3 are normally coexpressed on IL-3-responsive cells and have identical qualitative signaling capacities. Receptor transmodulation studies on bone marrow cells from wild-type, beta c -/-, and beta IL-3 -/- mice showed that the previously described hierarchical pattern of transmodulation was dependent on the relative numbers of both beta IL-3 and beta c receptor chains and also provided evidence for an unexpected interaction between beta c chains and G-CSF and M-CSF receptors.
Nicola
N A
NA
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Robb
L
L
Metcalf
D
D
Cary
D
D
Drinkwater
C C
CC
Begley
C G
CG
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism*; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016185:Receptors, Interleukin-3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D016185:Receptors, Interleukin-3