Table 1.
Summary of caspase-deficient mouse phenotypes
| Caspase | Mouse mutant phenotype | Function derived from deficient phenotype | References |
|---|---|---|---|
| Caspase-1 | Develop normally; have no defects in apoptosis | Are more susceptible to virus infection (Thomas et al. 2009); show enhanced tumor formation (Hu et al. 2010); have reduced apoptosis in several models such as neuronal cell death, myocardiac infarct, and heart failure (Frantz et al. 2003; Arai et al. 2006; Merkle et al. 2007); caspase-1-deficient mice are protected against cisplatin-induced apoptosis and acute tubular necrosis (Faubel et al. 2004) | Kuida et al. 1995; Li et al. 1995; Thomas et al. 2009; Hu et al. 2010 |
| Caspase-2 | Develop normally and are fertile; have only minor apoptotic defects in some cell types; MEFs show resistance to killing by HS and specific drugs | Caspase-2 has been proposed to be involved in different proapoptotic pathways, but the data from the gene-deficient mice do not support the majority of the in vitro results | Bergeron et al. 1998; O’Reilly et al. 2002; Tu et al. 2006 |
| Caspase-3 | Mice die perinatally in mixed background; some can survive to adulthood; show brain hyperplasia | Essential for neuronal cell death; caspase-3 is an essential component in some apoptosis pathways, dependent on the stimulus and cell type; essential for the regulation of B-cell homeostasis | Kuida et al. 1996; Woo et al. 1998, 2003 |
| Caspase-6 | Develop normally | No apoptotic defects | Unpublished (see Zheng et al. 1999) |
| Caspase-7 | Develop normally | No apoptotic defects | Lakhani et al. 2006 |
| Caspase-8 | Embryonic lethal; defects in heart muscle development |
Cells from caspase-8-deficient mice are resistant to death-receptor-induced apoptosis; inactivating mutation in humans shows immunodeficiency; tissue-specific deletion of caspase-8 revealed functions in T-cell homeostasis, in the generation of myeloid and lymphoid cells and the differentiation into macrophages, and in skin inflammation and wound healing; suppresses RIPK3-dependent necrosis | Juo et al. 1998; Varfolomeev et al. 1998; Chun et al. 2002; Salmena et al. 2003; Kang et al. 2004; Beisner et al. 2005; Kovalenko et al. 2009; Lee et al. 2009a; Li et al. 2010; Kaiser et al. 2011; Oberst et al. 2011; Zhang et al. 2011 |
| Caspase-9 | Perinatal lethal, but not 100% penetrant | Brain hyperplasia caused by decreased apoptosis and excess neurons; cells from caspase-9-deficient mice show resistance to apoptosis induced by a variety of cytotoxic drugs and irradiation | Hakem et al. 1998; Kuida et al. 1998 |
| Caspase-10 | No mouse homolog | Human inactivating mutations are associated with ALPS II | Wang et al. 1999 |
| Caspase-11 | Develop normally and are fertile | Mutant mice are resistant to endotoxic shock induced by LPS; IL-1 production after LPS stimulation is blocked; is necessary for caspase-1 activation; regulates cell migration in lymphocytes | Wang et al. 1998; Li et al. 2007 |
| Caspase-12 | Develop normally | Mice are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis in response to other death stimuli; thus, caspase-12 mediates an ER-specific apoptosis pathway; show an enhanced bacterial clearance and are more resistant to sepsis | Nakagawa et al. 2000; Saleh et al. 2006 |
| Caspase-14 | Develop normally and are fertile; their long-term survival was indistinguishable from that of wild-type mice | Mice show increased sensitivity to UVB irradiation; caspase-14-deficient epidermal cells show no defect in apoptosis; caspase-14 is responsible for the correct processing of (pro)filaggrin during cornification | Denecker et al. 2007 |
MEF, mouse embryonic fibroblast; HS heat shock; ALPS, autoimmune lymphoproliferative syndrome; LPS, lipopolysaccharide; ER, endoplasmic reticulum; RIPK3, receptor-interacting serine/threonine-protein kinase 3.