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
- Author(s)
- Nicola, NA; Robb, L; Metcalf, D; Cary, D; Drinkwater, CC; Begley, CG;
- Details
- Publication Year 1996-04-01,Volume 87,Issue #7,Page 2665-2674
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- 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 (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. (C) 1996 by The American Society of Hematology.
- Publisher
- W B SAUNDERS CO
- Keywords
- COLONY-STIMULATING FACTOR; GM-CSF RECEPTOR; MONOCLONAL-ANTIBODIES; EXPRESSION CLONING; HUMAN EOSINOPHILS; MACROPHAGE; BINDING; SUBUNIT; PROTEIN; RECONSTITUTION
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Creation Date: 1996-04-01 12:00:00