Table 2.

Role of DUSPs in the heart from knockout and transgenic mouse studies

DUSP	MAPK activity in KO mice	Phenotype of KO mice	MAPK activity in Tg mice	Phenotype of Tg mice	References
DUSP1	No change in ERK1/2, JNK, and p38 in fibroblasts	Greater infarction injury following I/R; hypertension following endotoxin treatment	Reduced activity of ERK1/2, JNK, and p38	Dilation, attenuated hypertrophy, increased apoptosis	[57, 58, 60, 62, 63]
DUSP4	Increased p38 activity	Cardiomyopathy in Dusp1/4−/− mice	Reduced ERK1/2 activity	Cardiac hypertrophy and impaired function	[59, 71]
DUSP6	Increased ERK1/2 activity at baseline	Increased myocyte proliferation; Increased heart weight; protected from decompensation following prolonged TAC	Reduced ERK1/2 activity	Decompensation, increased fibrosis and apoptosis following prolonged TAC	[79, 45]
DUSP8	Increased ERK1/2 activity at baseline and following stimulation	Concentric remodeling; increased contractility; protected from injury	Reduced activity of ERK1/2, p38 and JNK	Dilation, fibrosis and cardiac dysfunction	[28]
DUSP14	Increased activity of p38 and JNK following TAC	Hypertrophy, fibrosis, dilation, dysfunction following TAC	Decreased activity of p38 and JNK following TAC	Attenuated TAC-induced cardiac dysfunction and remodeling	[27]

Abbreviations: DUSP, dual-specificity phosphatase; ERK, extracellular signal-regulated kinase; I/R, ischemia-reperfusion; JNK, c-Jun N-terminal kinase; KO, knockout; MAPK, mitogen-activated protein kinase; TAC, transverse aortic constriction; Tg, transgenic.