Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor β-chain: Implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells

Abstract

The receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 and -5 (IL-3, IL-5) share a common signaling subunit (βc). However, in the mouse, IL-3 can also use an alternative IL-3-specific receptor β-chain (βIL-3). To assess the relative contributions of βc and βIL-3 to IL-3 receptor formation and function, mice were generated in which the βIL-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 βc and βIL-..