Table 1. Mouse models and their outcomes of JNK pathway deficiency.

Disorder	Mouse model	Tissue	Outcome	References
Obesity/IR	Jnk1−/−	Whole body	JNK1-deficient mice were protected from obesity and insulin resistance	[29,30]
	Mlk2−/−Mlk3−/−	Whole body	The sympathoadrenal system contributes to the increased energy expenditure in MLK-deficient mice	[8, 9]
	Jip1−/−	Whole body	Jip deficiency decreased inhibitory phosphorylation of IRS-1 on Ser307 and therefore increased insulin sensitivity	[31]
	Jnk1−/−	Adipocyte	Mice with Jnk1-deficient adipocytes exhibit dramatically improved hepatic insulin sensitivity partially through less IL6 production by adipocytes	[30,32]
	Jnk1−/−	Liver	Promotes insulin resistance	[30,33]
	Jnk1−/− Jnk2−/−	Liver	JNK-mediated inhibition of hepatic FGF21 promotes insulin resistance	[34]
	Jnk1−/−	Muscle	Reduced muscle LPL expression might contribute to the increased muscle insulin sensitivity in JNK1-deficient mice	[30,35]
	Jnk1−/−	Brain	Nervous system Jnk1 deficiency caused increased expression of thyrotropin releasing hormone (TRH) in the hypothalamus, thyroid stimulating hormone (TSH) by the pituitary gland, and increased circulating levels of thyroid hormones (T3 and T4) in the blood. Thus hypothalamic–pituitary–thyroid axis is a crucial target of JNK1 that controls obesity	[30,36,37]
	Jnk1−/− Jnk2−/−	Anterior pituitary gland	JNK-dificient mice exhibited an increase in the pituitary expression of thyroid-stimulating hormone (TSH)	[38]
	Jnk3−/−	AgRP neuron	JNK3 deficiency causes hyperphagia selectively in high-fat diet (HFD)-fed mice	[39]
	Jnk1−/− Jnk2−/−	Monocytes	JNK was necessary for pro-inflammatory macrophage (M1) polarization	[40]
	Jnk1−/−	Pancreatic b cells	JNK1 inhibits glucose-induced insulin production	[41]
Atherosclerosis	Jnk1−/−	Endothelium	JNK1 required for apoptosis and atherosclerosis	[42]
	Jnk1−/−	Bone marrow transplant	JNK1 deficiency promotes disease	[43]
	Jnk2−/−	Whole body	JNK2 deficiency reduced SR-A receptors endocytosis, therefore, less foam cell formation	[44]
Abdominal aortic aneurysm	SP600125/Jnk2−/−	Whole body	JNK2 deficiency reduced secretion of MMP-9 and MMP-2 from VSMCs, THP-1 macrophages	[45]
Myocardial infraction	Jnk1−/−		Pro-survival role when the period of ischemia is brief and injurious when the period of ischemia is extended	[46]
	Ask1−/−	Whole body	Protection	[47–49]
Peripheral artery disease (PAD)	Jnk1−/− Jnk2−/−	Endothelium	JNK deficiency promotes PAD	[50]