Table 3.

Phenotypes of mice lacking initiator caspases. *Mutation in self processing site, d.p.c. day post coitum, HFSC hair follicle stem, NGF nerve growth factor

	mouse strain	development/ phenotype	apoptotic/ non-apoptotic/unspecified effect	reference
Casp-2 −/−	C57BL/6J	normal development	decreased number of oocytes, increased number of motoneurons	[46]
Casp-2 −/−	129/sv×C57BL/6	normal development	normal apoptosis of thymocytes induced by various stimuli, normal apoptosis of neurons in absence of NGF	[70]
Casp-2 −/−	C57BL/6J	reduced sensitivity to heat-shock	reduced cell death	[296]
Casp-2 −/−	C57Bl/6	premature ageing	compromised ability to clear oxidatively damaged cells	[67]
Casp-2 −/− /MMTV	129/B6	increased tumor acquisition	cell cycle defects, genomic instability	[75]
Casp-2 −/−	C57BL/6J	premature ageing	increased oxidative stress	[15]
Casp-2 −/−	C57BL/6J	age-related bone loss	increased number of osteoclasts due to reduced apoptosis and increased differentiation	[71, 72]
Casp-2 −/−	C57BL/6J	reduced white adipose mass, smaller white adipocytes etc.	altered balance in fuel choice towards increased carbohydrate utilisation due to mild energy stress	[76]
Casp-8 −/−	C57BL/6	abnormalities of heart etc.-prenatally lethal	abnormal receptor-dependent pathway of apoptosis	[68]
Casp-8 −/− (conditional T-cells-specific)	C57BL/6	inability of immune response to viral infection	resistance of T-cells to death mediated by anti-CD95 antibody	[90]
Casp-8−/−(conditional-several types)	MF-1	lethal/ non-lethal phenotypes	apoptotic/non-apoptotic engagement in dependence of the targeted cells	[97]
Casp-8 −/− (conditional B cells-specific)	-	altered responses of B cells to different stimuli	B cells: abrogation of Fas-mediated apoptosis, failure of induced proliferation, altered ab production	[91]
Casp-8 −/− (conditional B cells-specific)	129/J × C57BL/6	normal cell subpopulations in bone marrow	resistance to DR mediated apoptosis, defective B cells expansion response to TLR4 stimulation, attenuated antibody production upon viral infection	[105]
Casp-8 −/− (conditional keratinocytes-specific)	C57BL/6	inflammatory diseases of the skin-lethal by postnatal day 7	constitutive phosphorylation of interferon regulatory factor (irf) 3 and tank-binding	[94]
Casp-8 −/− (conditional epidermis-specific)	-	epidermal hyperplasia	increased stem cell proliferation and cutaneous inflammation regulated by il-1α	[102]
Casp-8 −/− (conditional hepatocytes-specific)	-	abnormal hepatocyte reaction to damage	apoptotic and non-apoptotic mechanisms of response to different stimuli	[106, 107]
Casp-8 −/− (conditional macrophage-specific)	C57BL/6	mild systemic inflammatory disease	unchecked ripk3 activity	[101]
Casp-8-/- (conditional endothelium -specific)	-	reduced retina angiogenesis	reduced endothelial proliferation, sprouting, and migration, destabilization cadherin	[32]
Casp-8−/−D387A*	C57BL/6	normal development	reduced Fas-induced apoptosis of T cells, preservation of fas-mediated non-apoptotic signalling	[97]
Casp-9 −/−	129/C57BL/6 129/CD1	severe brain defect-prenatally lethal	resistance of different cells to apoptotic stimuli	[124]
Casp-9 −/−	C57BL/6	severe brain malformation- prenatally lethal	reduced apoptosis and activation of caspase-3 in brain, resistance of T cells to different apoptotic stimuli	[69]
Casp-9 −/−	C57BL/6	defects and size reduction of the inner ear	decrease of Apaf-1 dependent apoptosis	[116]
Casp-9 −/−	C57BL/6	misrouted axons	abnormal cleavage of sema7a	[122]
Casp-9 −/−	C57BL/6	increased number of oocytes	decreased apoptotic elimination of oocytes during a narrow window between 18.5 and 21.5 d.p.c.	[125]
Casp-9 −/− (conditional HFSC-specific)	-	accelerated wound repair	induction of apoptotic-engaged state, serving as mitogenic signalling centres by releasing wnt3	[129]