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Analysis of hematopoiesis in max 41 transgenic mice that exhibit sustained
elevations of blood granulocytes and monocytes
D Metcalf, GJ Lindeman and NA Nicola
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne
Hospital, Victoria, Australia.
An unusual mouse line (max 41) that carries an inserted transgene encoding
the nuclear transcription factor, Max, exhibits a 50- to 60- fold elevation
of blood neutrophils and a 10-fold elevation of blood monocytes. Analysis
showed that these elevated levels of blood cells were sustained
incrementally by a sevenfold increase in mature neutrophils in the bone
marrow and spleen and a fourfold increase in granulocyte-committed
progenitor cells with normal turnover times for mature neutrophils and
monocytes in the marrow and blood. the progenitor cells were not autonomous
and exhibited a normal quantitative responsiveness to stimulation in vitro
by the four colony- stimulating factors. A consistent anomaly noted was
that, when stimulated by macrophage colon-stimulating factor, max 41
progenitor cells formed mainly granulocyte-containing colonies, rather than
the usual macrophage colonies. The blast colony-forming cells from max 41
mice did not generate abnormal numbers or types of progenitor cells. The
transgenic max 41 model requires further analysis to establish the
regulatory anomaly responsible for the excessive production of granulocytes
and monocytes, but has emphasized that most neutrophils generated in the
marrow normally never leave the organ.
Volume 85,
Issue 9,
pp. 2364-2370,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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