Table 1:

Consequence of the genetic manipulation of ISR components in mice

Member	Model	Development	Phenotypes	Ref.
ATF4	CREB−/−	Retarded	Defective lens development, and microphthalmia Anemia Dwarfisms and severe skeletal abnormalities	30, 59, 174, 176, 177
	CREB+/−	Normal	No specific phenotype
	CREB−/− and P53−/−double KO	--	Normal eye morphology, lower number of lens fibers
GCN2	GCN2−/−	Normal	Developmental delay occurred if being fed with leucine deficit diet	178
HRI	HRI−/−	Normal	Macrocytosis and hyperchromia	51
PKR	Pkr−/−	Normal	No specific phenotype	179
PERK	Perk−/−	Retarded	Impaired insulin secretion and hyperglycemia; Growth retardation and abnormal bone development	180–183
	Perk−/−	--	Acute diabetes	194
	Perk loxP/loxP & CamkIIα-Cre	--	Behavior change	184
GADD34	GADD34−/−	Normal	No signs of disease or abnormal phenotypes at least the first 12 months of life	145
CReP	Ppp1r15b−/−	Retarded	Half size, pale skin, impaired erythropoiesis, fail to survive in postnatal day 1	186
	Ppp1r15b+/−	Normal	No specific phenotype
EIF2α	Homozygous non-phosphorylatable KI (S51A)	Lethal	Severe hypoglycemia. Lethal within 24 hours of birth.	188
	Heterozygous non-phosphorylatable KI (S51A)	Normal	Glucose intolerance, increased weight gain if been fed with high fat diet, pancreatic β-cell failure.	189
	Conditional β-cell specific KO	--	Decreased insulin secretion, type 2 DM	190
CHOP	CHOP−/−	Normal	Reduced performance in memory-related behaviors	192

KO: knock out; KI: knock in