Transgenic mice expressing antisense interleukin-3 RNA develop a B-cell
lymphoproliferative syndrome or neurologic dysfunction
DA Cockayne, DM Bodine, A Cline, AW Nienhuis and CE Dunbar
Clinical Hematology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD.
Transgenic mice that expressed antisense interleukin-3 (AS-IL-3) RNA were
generated and exhibited either a B-cell lymphoproliferative syndrome or
progressive neurologic dysfunction. Each syndrome occurred in the founder
or progeny mice of three separate transgenic lines. The lymphoproliferative
process involved the accumulation, within peripheral lymphoid organs, of
B220+/slgM- pre-B cells that had immunoglobulin (Ig) genes predominantly in
germline configuration and expressed lambda 5 and Rag-1 transcripts.
Transgenic animals that developed neurologic dysfunction exhibited circling
behavior that progressed to ataxia and terminal inanition. AS-IL-3
transcripts were detected in mature CD3+ T cells of asymptomatic transgenic
animals, as well as in B220+/slgM- pre-B cells, and CD3+ T cells from
animals with the lymphoproliferative syndrome. AS-IL-3 transcripts were
also detected in the brains of both young asymptomatic transgenic animals
and older transgenic animals with neurologic dysfunction. Decreased IL- 3
production from ConA-stimulated splenocytes was observed in asymptomatic
transgenic animals. These observations suggest that this cytokine may have
important roles in B lymphopoiesis and neurologic function.
Volume 84,
Issue 8,
pp. 2699-2710,
10/15/1994
Copyright © 1994 by The American Society of Hematology
