Mice lacking both macrophage- and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease

Blood. 1994 Jul 1;84(1):27-35.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blood Cell Count
  • Granulocyte-Macrophage Colony-Stimulating Factor / deficiency*
  • Interleukin-3 / physiology
  • Lung / pathology
  • Lung / ultrastructure
  • Lung Diseases / etiology*
  • Macrophage Colony-Stimulating Factor / deficiency*
  • Macrophages / pathology*
  • Mice
  • Molecular Sequence Data
  • Osteopetrosis / etiology*

Substances

  • Interleukin-3
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor