Table 2.

Phenotypes of mice deficient in caspase or caspase adapter proteins

Gene Development Phenotype Reference
Caspase-1 NormalDefective lipopolysacharide-induced secretion of IL-1α and β and γ interferon; resists endotoxic shock; thymocytes partially resistant to Fas-mediated apoptosis111, 123
Caspase-2 Normal Increased number of oocytes at birth, and oocytes less susceptible to doxorubicin-induced apoptosis; B cells partially resistant to death induction by granzyme B; accelerated apoptosis of facial motor neurons4
Caspase-3 Perinatally lethal Ectopic brain tissue; ES resistant to UV and osmotic shock-induced apoptosis; sensitivity to γ-irradiation unaffected; peripheral T cells partially resistant to anti-CD-3ε and Fas-induced apoptosis; transformed EF cells less susceptible to adriamycin, TNF-α, and low serum; abnormal chromatin condensation and no DNA fragmentation in dying cells 112, 236
Caspase-8 Embryonically lethal at approx. E12.5 Abnormal heart development and vascular hyperemia; EF resistant to Fas, TNF-α, and DR3 but exhibit normal sensitivity to UV, etoposide, low serum, and staurosporine; death receptor signaling to JNK and NF-κB intact219
Caspase-9 Embryonically lethal at approx. E16.5Ectopic brain tissue; ES cells resistant to adriamycin, UV, and γ-irradiation; EF resistant to UV and DNA-damaging agents but not to TNF-α; thymocytes resistant to etoposide, dexamethasone, and γ-irradiation, but sensitive to UV and Fas; loss of mitochondrial potential and procaspase-3 processing blocked, but cytochromec release unaffected 76, 110
Caspase-11 NormalResistant to lipopolysaccharide-induced caspase-1 processing, IL-1α and -β secretion, and endotoxic shock 226
Caspase-12Normal EF partially resistant to ER stress such as tunicamycin and thapsigargin; cortical neurons resistant to β-amyloid-induced apoptosis 149
Apaf-1 Embryonically lethal at approx. E16.5Ectopic brain tissue; craniofacial developmental anomalies; transient persistence of interdigital webs; ES and EF resistant to UV, DNA-damaging agents, and γ-irradiation; thymocytes and peripheral activated T cells resistant to many stimuli but not to Fas; defective processing of procaspase-2, -3, and -8 during thymocyte apoptosis induced by dexamethasone or etoposide; loss of mitochondrial potential but not cytochrome c release 16, 252
FADDEmbryonically lethal at approx. E9-E12.5 Abnormal heart development and hemorrhage; no mature B cells and defective T-cell activation; EF and thymocytes resistant to Fas and TNF-α but normal sensitivity to E1A, myc, and adriamycin 249, 257