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Mice lacking both macrophage- and granulocyte-macrophage colony-
stimulating factor have macrophages and coexistent osteopetrosis and severe
lung disease
GJ Lieschke, E Stanley, D Grail, G Hodgson, V Sinickas, JA Gall, RA Sinclair and AR Dunn
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research,
Royal Melbourne Hospital, Victoria, Australia.
Mice deficient in granulocyte-macrophage colony-stimulating factor (GM-
CSF) and macrophage colony-stimulating factor (M-CSF, CSF-1) were generated
by interbreeding GM-CSF-deficient mice generated by gene targeting
(genotype GM-/-) with M-CSF-deficient osteopetrotic mice (genotype M-/-,
op/op). Mice deficient in both GM-CSF and M-CSF (genotype GM-/-M-/-) are
viable and have coexistent features corresponding to mice deficient in
either factor alone. Like M-CSF- deficient mice, they have osteopetrosis
and are toothless because of failure of incisor eruption. Like
GM-CSF-deficient mice, they have a characteristic alveolar-proteinosis-like
lung pathology, but it is more severe than that of GM-CSF-deficient mice
and is often fatal. In particular, in GM-/-M-/- mice the accumulation of
lipo-proteinaceous alveolar material is more marked, and bacterial
pneumonic infections are more prevalent and more extensive, particularly
involving Gram- negative bacteria. Neutrophilia consistently accompanies
pulmonary infections, and some older GM-/-M-/- mice have polycythemia.
Survival of GM-/-M-/- mice is significantly reduced compared with mice
deficient in either factor alone, and all GM-/-M-/- mice have broncho- or
lobar- pneumonia at death. These observations indicate that in vivo, M-CSF
is involved in modulating the consequences of GM-CSF deficiency in the
lung. Interestingly, GM-/-M-/- mice have circulating monocytes at levels
comparable with those in M-CSF-deficient mice and the diseased lungs of all
GM-/-M-/- mice contain numerous phagocytically active macrophages,
indicating that in addition to GM-CSF and M-CSF, other factors can be used
for macrophage production and function in vivo.
Volume 84,
Issue 1,
pp. 27-35,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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