Targeted disruption of SPI3/Serpinb6 does not result in developmental or growth defects, leukocyte dysfunction, or susceptibility to stroke
| Autor: | Harshal Hanumant Nandurkar, Peter J Crack, Kheng Sok Ung, Catherina H. Bird, Phillip I. Bird, Katrina Louise Scarff |
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| Rok vydání: | 2004 |
| Předmět: |
Recombinant Fusion Proteins
Cathepsin G Biology Serpin Granulocyte Brain Ischemia chemistry.chemical_compound Mice medicine Leukocytes Mammalian Genetic Models with Minimal or Complex Phenotypes Animals Humans Tissue Distribution Candida albicans Molecular Biology Serpins Mice Knockout Monocyte SERPINB1 Candidiasis Cell Biology biology.organism_classification Stroke medicine.anatomical_structure chemistry Neutrophil elastase Plasminogen activator inhibitor-2 Immunology Gene Targeting biology.protein Disease Susceptibility Peritoneum |
| Zdroj: | Molecular and cellular biology. 24(9) |
| ISSN: | 0270-7306 |
| Popis: | Protease inhibitor 6 (PI-6/SERPINB6) is a widely expressed nucleocytoplasmic serpin. It inhibits granulocyte cathepsin G and neuronal neuropsin, and it is thought to protect cells from death caused by ectopic release or internalization of protease during stress such as infection or cerebral ischemia. To probe the biological functions of PI-6, we generated mice lacking its ortholog (SPI3/Serpinb6). SPI3-deficient mice developed normally and were fertile, and no abnormal pathology or increased sensitivity to cerebral ischemia was observed. There were no perturbations in leukocyte development or numbers, and recruitment of leukocytes to the peritoneal cavity was normal. SPI3-deficient mice were equally susceptible as wild-type mice to systemic Candida albicans infection, although there was a slight decrease in the ability of neutrophils from SPI3-deficient mice to kill C. albicans in vitro. Increased levels of a related inhibitor Serpinb1 (monocyte/neutrophil elastase inhibitor) in the tissues of targeted mice suggests that compensation by other serpins reduces the impact of SPI3 deficiency in these animals and may explain the lack of a more obvious phenotype. |
| Databáze: | OpenAIRE |
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