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Updated: Aug 7, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Normal neutrophil function in cathepsin G-deficient mice
D M MacIvor1, S D Shapiro, C T Pham
1Department of Internal Medicine, Division of Bone Marrow Transplantation and Stem Cell Biology, Washington University Medical School, St. Louis, MO 63110, USA.
Abstract:
Cathepsin G is a neutral serine protease that is highly expressed at the promyelocyte stage of myeloid development. We have developed a homologous recombination strategy to create a loss-of-function mutation for murine cathepsin G. Bone marrow derived from mice homozygous for this mutation had no detectable cathepsin G protein or activity, indicating that no other protease in bone marrow cells has the same specificity. Hematopoiesis in cathepsin G-/- mice is normal, and the mice have no overt abnormalities in blood clotting. Neutrophils derived from cathepsin G-/- mice have normal morphology and azurophil granule composition; these neutrophils also display normal phagocytosis and superoxide production and have normal chemotactic responses to C5a, fMLP, and interleukin-8. Although cathepsin G has previously shown to have broad spectrum antibiotic properties, challenges of mice with Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli yielded survivals that were not different from those of wild-type animals. In sum, cathepsin G-/- neutrophils have no obvious defects in function; either cathepsin G is not required for any of these normal neutrophil functions or related azurophil granule proteases with different specificities (ie, neutrophil elastase, proteinase 3, azurocidin, and/or others) can substitute for it in vivo.
Insights
Mice lacking the neutral serine protease cathepsin G show normal hematopoiesis and neutrophil function. This suggests cathepsin G is not essential for these processes, or other proteases compensate for its absence.
Area of Science:
- Immunology
- Hematology
- Biochemistry
Background:
- Cathepsin G is a neutral serine protease abundant in myeloid cells.
- Its precise in vivo functions remain incompletely understood.
- Developing genetic models is crucial for dissecting protease roles.
Purpose of the Study:
- To investigate the in vivo function of cathepsin G.
- To determine if cathepsin G is essential for neutrophil functions and host defense.
- To create and characterize a murine model of cathepsin G deficiency.
Main Methods:
- Homologous recombination was used to generate a loss-of-function mutation for murine cathepsin G.
- Cathepsin G protein and activity were assessed in bone marrow.
- Phenotypic analysis of cathepsin G-/- mice included hematopoiesis, blood clotting, neutrophil morphology, phagocytosis, superoxide production, chemotaxis, and bacterial challenge.
Main Results:
- Cathepsin G deficient mice (cathepsin G-/-) exhibited no detectable cathepsin G protein or activity in bone marrow.
- Hematopoiesis and blood clotting were normal in cathepsin G-/- mice.
- Neutrophils from cathepsin G-/- mice showed normal morphology, granule composition, phagocytosis, superoxide production, and chemotaxis.
- Cathepsin G-/- mice survival rates were similar to wild-type controls when challenged with Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli.
Conclusions:
- Cathepsin G is not essential for normal hematopoiesis, blood clotting, or key neutrophil functions in vivo.
- The absence of cathepsin G did not impair host defense against common bacterial pathogens.
- Related proteases may compensate for cathepsin G's function, or its role in these specific processes is redundant.
