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Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast
cells
J Domen, NM van der Lugt, PW Laird, CJ Saris, AR Clarke, ML Hooper and A Berns
Division of Molecular Genetics, The Netherlands Cancer Institute,
Amsterdam.
The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific
protein kinases. The gene has been found to be activated (overexpressed) by
retroviral insertion in hematopoietic tumors in mice. Transgenic mice that
overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell
lymphomas and an increased susceptibility to Moloney murine leukemia virus
and N-ethyl-N- nitrosourea-induced lymphomas. Apart from a slight
enlargement of the spleen, no abnormalities were found in prelymphomatous
transgenic mice. Inactivation of the Pim-1 gene in the germline of mice
resulted in mice with a surprisingly subtle phenotype. Therefore, we
investigated whether subtle effects of the absence of Pim-1 could be made
visible during in vitro culturing of hematopoietic cells. We found that
bone marrow-derived mast cells (BMMC) lacking Pim-1 had a distinct growth
disadvantage when grown on interleukin (IL)-3, but not when stimulated by
the factors IL-4, IL-9, or Steel factor (SF). This indicates a role for
Pim-1 as a modulator of the IL-3 signal transduction pathway.
Volume 82,
Issue 5,
pp. 1445-1452,
09/01/1993
Copyright © 1993 by The American Society of Hematology
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