Table 1. Phenotypes of p38 and p38global and tissue-specific deficient mice.

Mice / In vivophenotype / In vitrophenotype / Reference
Disease / model / readout / Cell/stimuli / readout
p38-/- / Sepsis / LPS-Dgal / ⇄survival; ⇄TNF, IL6, IL10, IL1, IL1, IL12 and GM-CSF / Macrophage / LPS / ⇄TNF, IL6, IL10 and IL12; ↓IL1 / [4]
Arthritis / CIA / ↓arthritis / [24]
Skin Tumour/ DMBA/TPA / ↓tumours / [13]
Skin inflammation/ TPA / ↓proliferation; ⇄TNF, IL1, IL6 and TGF / [13]
CAC / AOM/DSS / ↓tumours / [17]
Physiological hypertrophy / heart growth / ↓heart size / [41]
Pathological hypertrophy / Angiotensin II / ↓heart hypertrophy; ↓cardiomyocyte size / [41]
Non-alcoholic fatty liver disease(NAFLD)/ MCD diet / ↑ALT / [18]
Excitotoxicity/pentylenetetrazole / ↑ excitotoxic seizures / [53]
p38 flox/flox LysM Cre / Liver damage / LPS-Dgal / ⇄survival; ↓ liver haemorrhage; ⇄liver apoptosis ↓AST and ALT / [7]
p38 flox/flox Villin Cre / CAC / AOM/DSS / ↓tumour / [39]
Colitis / DSS / ↓TNF, IL-6, IL-1 / [39]
APP23.p38-/- / Alzheimer’s Disease/
Amyloid-ß overexpression / ↑ premature mortality; ↑ excitotoxic seizures; ↑ spontaneous epileptiform activity; ↑ memory deficits; ↑ neuronal network dysfunction;
⇄ Amyloid-ß pathology / [53]
APP23.p38-/-tau-/- / AD/ Amyloid-ß overexpression
Absence of Tau / Negative effects in APP23p38-/-abolished / [53]
Alz17.p38-/- / Axonopathy, nerve dysfunction/ Tau overexpression / ↑↑excitotoxic seizures / [53]
tau-/-p38-/- / Tau absence / ↓ excitotoxic seizures / [53]
Tg.p38-CA / Constitutively active human p38 D179A in neurons / ↓excitotoxic seizures / [53]
APP23.Tg p38-CA / Alzheimer’s Disease/
Amyloid-ß overexpression, constitutively active human p38 D179A in neurons / ↓memory deficits; ↓ network aberrations / [53]
p38-/- / Sepsis / LPS-Dgal / ⇄survival; ⇄TNF, IL-6, IL10, IL1, IL1, IL12 and GM-CSF / Macrophage / LPS / ⇄TNF, IL-6, IL10 and IL12; ↓IL1 / [4]
Arthritis / CIA / ↓arthritis / [24]
Skin inflammation/ TPA / ↓proliferation; ⇄TNF, IL1, IL6 and TGF / [13]
Skin Tumour/ DMBA/TPA / ↓tumours;
long termDMBA/TPA:↓proliferation;
short term DMBA/TPA:↑ TNF, IL1, IL6, IL10 S100A8 and S100A9, ↑epidermal thickness / [13]
[36]
[37]
CAC / AOM/DSS / ↓tumours / [17]
Physiological hypertrophy / heart growth / ↓heart size / [41]
Pathological hypertrophy / Angiotensin II / ↓heart hypertrophy; ↓cardiomyocyte size / [41]
NAFLD/ MCD diet / ↑ALT; ↓circulating neutrophils / [18]
Acute lung inflammation (ALI)/ LPS / ↓lung damage; ↓lung inflammation; ↓neutrophil extravasation and chemotaxis / Neutrophils / fMLP / ↓adhesion; ↓transmigration; ↓chemotaxis / [14]
Bacterial infection/ E. coli / ↑bacterial infection / [14]
Diabetes-Insulin resistance/ Glucose / ↑glucose tolerance; ↑insulin secretion from pancreatic  cell / [15]
Diabetes / HFD / ↑glucose tolerance; ↑insulin secretion from pancreatic  cell; ↓ insulin resistance / [15]
Pancreatic  cell failure/ streptozotocin / ↑insulin secretion; ↓ cell failure / [15]
Tracheal epithelial cells / IL13 / ⇄ mClca3, Muc5ac / [19]
p38δ-/-;
K-RasG12D+/- / Oncogenic mutation of K-Ras / ↓lung tumours / [36]
p38 flox/flox LysM Cre / Acute lung inflammation (ALI)/ LPS / ↓neutrophil in bronchoalveolar lavage / Neutrophils / fMLP / ↓transmigration / [14]
Liver damage / LPS-Dgal / ↑survival;↓ liver haemorrhage; ↓liverapoptosis; ↓AST, ALT, TNF IL6, MIP1 and MIP1 / [7]
p38 flox/flox Mck Cre / Physiological hypertrophy / ↓heart size / [41]
p38 flox/flox Mrp8 Cre / NAFLD/ MCD diet / ↓steatohepatitis; ↓ALT;↓liver neutrophil recruitment / [18]
p38/-/- / Sepsis / LPS-Dgal / ↑survival; ↓TNF, IL6, IL10, IL1 and IL1; ⇄IL12 and GM-CSF / Macrophages / LPS / ↓TNF, IL1 and IL10; ⇄IL6; ↑IL12, IFN
DC / LPS / ↓TNF, IL1 and IL10; ⇄IL6; ↑IL12 / [4]
Arthritis / CIA / ↓↓arthritis; ↓clinical score; ↓bone destruction; ↓anti-collagen antibodies, ↓IL1 TNF, IL17 and IFN, ⇄IL6; ↓Th17 cells / T cell / CII
T cell / CD3 / ↓proliferation, ↓TNF, IL17 and IFN; ⇄IL1
↓proliferation, ↓IL17 and IFN; ⇄TNF andIL1 / [24]
Skin Tumour/ DMBA/TPA / ↓↓tumours; ⇄apoptosis; ⇄DNA damage / [13]
Skin inflammation/ TPA / ↓↓proliferation;↓IL1 TNF, IL6, KC and MIP2⇄TGF; ⇄ Macrophage,  T cell and CD3+ cell recruitment; ↓neutrophil recruitment / Keratinocyte / TPA / ↓IL1, IL6 and KC; ⇄MIP2 and TGF / [13]
CAC / AOM/DSS / ↓↓tumours; ↓TNF and COX2; ⇄IL1IL6, IL10 and HGF; ↓ulcer size / [17]
Colitis / DSS / ↓proliferation, ↑apoptosis; ↓TNF, IL1IL6, MIP2, KC, MCP1and COX2; ⇄IL10, IL12, CCR1, CCR2 and CCR5;↑IFNand IL17A; ↓neutrophil and macrophage recruitment; ⇄ Treg, CD4+ and CD8+ cell recruitment / [17]
Physiological hypertrophy / heart growth / ↓heart size / Mouse embryonic fibroblasts (MEF) / ↓cell size and protein synthesis / [41]
Pathological hypertrophy / Angiotensin II / ↓heart hypertrophy; ↓cardiomyocyte size / [41]
NAFLD/ MCD diet / ↓steatohepatitis and fibrosis; ↓TNF and IL-6; ↓neutrophil and macrophage recruitment / [18]
p38/ flox/flox LysM Cre / Skin inflammation/ TPA / ⇄IL1 TNF, IL6 and KC / [13]
Liver damage / LPS-Dgal / ↑survival;↓ liver haemorrhage; ↓liverapoptosis; ↓AST, ALT, TNF IL6, MIP1 and MIP1; ↓neutrophil recruitment; ⇄macrophage and monocyte recruitment / Macrophages / LPS
Kupffer / LPS
Neutrophil / LPS / ↓TNF and IL6
↓TNF and IL6
↓TNF and IL6 / [7]
NAFLD/ MCD diet / ↓steatohepatitis; ↓liver TNF and IL-6;↓liver neutrophil and macrophage recruitment / [18]
NAFLD/ HFD diet / ↓steatohepatitis; ↑Glucose tolerance liver; ↓liver neutrophil recruitment / [18]
NAFLD/ HFF diet / ↓steatohepatitis / [18]

Other phenotypes found in cells from the different p38 and p38knockout mice are described either elsewhere [2, 39] or in the text. ↑ significant increase; ↓ significant decrease; ⇄ not significant change.ALT, alanine aminotransferase; AST, aspartate aminotransferase; CII, type II collagen; Dgal, D-galactosamine; HFD, high-fat diet; HFF, high-fat and high-fructose diet; MCD, methionine and choline deficient diet.

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