Analysis of hematopoiesis in max 41 transgenic mice that exhibit sustained elevations of blood granulocytes and monocytes

Abstract

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 colony-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.