Targeted disruption of SPI3/Serpinb6 does not result in developmental or growth defects, leukocyte dysfunction, or susceptibility to stroke.
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.
Scarff
Katrina L
KL
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Ung
Kheng S
KS
Nandurkar
Harshal
H
Crack
Peter J
PJ
Bird
Catherina H
CH
Bird
Phillip I
PI
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002177:Candidiasis / Q000378:metabolism; D004198:Disease Susceptibility; D018390:Gene Targeting; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010537:Peritoneum / Q000166:cytology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism*; D020521:Stroke / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D011993:Recombinant Fusion Proteins; D015843:Serpins; C094472:serpin B6