The Role of Suppressors of Cytokine Signalling in Human Neoplasms

Table 3

In vivo disorders resulting from SOCS proteins manipulation.

Gene	Knockout phenotype	Transgenic phenotype	Main affected cytokines	Reference
CIS	(?) Increased haematopoiesis, disturbed lactation, and increased susceptibility to infections with single nucleotide polymorphism (SNP) at CIS promoter position 292	Reduced weight, defective mammary gland development, altered T and NK cell responses	STAT5 signalling (GH, EPO, IL-2, IL-3, and PRL)	[37, 93, 94, 191]
SOCS1	Multiorgan inflammation, neonatal lethality, lymphocyte apoptosis, and haematopoietic infiltrations	Disturbed T-lymphocyte development and spontaneous T cell activation	IFN𝛾, IFN𝛼, IL-4, and IL-12	[57, 192–195]
SOCS2	Gigantism	Gigantism	GH and IGF-1	[79, 149, 163, 196–198]
SOCS3	Embryonic lethality, placenta defects, disturbed erythropoiesis, and enhanced response to G-CSF	Embryonic lethality, increased Th2 differentiation, and reduced pancreatic 𝛽 cell proliferation	gp130, IL-2, IL-6, G-CSF, leptin, and EPO	[94, 111, 199–203]
SOCS4	?	?	?
SOCS5	(?) No obvious phenotype (redundancy with SOCS4?)	Disturbed Th2 differentiation, increased peritoneal IL-2 and IFN𝛾, and decreased lethality from peritonitis	IL-4 and EGF	[129, 189, 204, 205]
SOCS6	Mild growth retardation (redundancy with SOCS7?)	Improved glucose and insulin tolerance	Insulin (?)	[129, 165, 204]
SOCS7	Hydrocephalus, 50% mortality, Hyperinsulinemia	?	Insulin	[130, 190]