Generation and characterization of Smac/DIABLO-deficient mice

Okada, H., Suh, W. K., Jin, J., Woo, M., Du, C., Elia, A., Duncan, G. S., Wakeham, A., Itie, A., Lowe, S. W., Wang, X., Mak, T. W. (May 2002) Generation and characterization of Smac/DIABLO-deficient mice. Molecular and Cellular Biology, 22 (10). pp. 3509-3517. ISSN 0270-7306

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URL: http://www.ncbi.nlm.nih.gov/pubmed/11971981
DOI: 10.1128/MCB.22.10.3509-3517.2002

Abstract

The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor of apoptosis proteins (IAPs). In response to apoptotic stimuli, Smac is released into the cytosol and promotes caspase activation by binding to IAPs, thereby blocking their function. These observations have suggested that Smac is a new regulator of apoptosis. To better understand the physiological function of Smac in normal cells, we generated Smac-deficient (Smac−/−) mice by using homologous recombination in embryonic stem (ES) cells. Smac−/− mice were viable, grew, and matured normally and did not show any histological abnormalities. Although the cleavage in vitro of procaspase-3 was inhibited in lysates of Smac−/− cells, all types of cultured Smac−/− cells tested responded normally to all apoptotic stimuli applied. There were also no detectable differences in Fas-mediated apoptosis in the liver in vivo. Our data strongly suggest the existence of a redundant molecule or molecules capable of compensating for a loss of Smac function.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: May 2002
Date Deposited: 31 Oct 2013 18:56
Last Modified: 31 Oct 2013 18:56
PMCID: PMC133802
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28762

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