Table 2.

Insights into DDR function from Knockout Mice and Mutations in Humans

	DDR1 knockout mice	DDR2 knockout mice	DDR2 mutations in mice (slie) and humans (SMED-SL)
Skeletal system	Smaller in size, poorly mineralized fibula bone [94].	Mouse: Dwarfism and shorter long bones due to reduced chondrocyte proliferation [118].	Mouse: Dwarfism [121]. Human: Multiple skeletal defects in SMED-SL (Short-limb abnormal calcification) [119], due to DDR2 trafficking defects or defects in collagen-binding activity [120].
Mammary Gland	Lactational defect, delayed mammary gland ductal outgrowth, hyper-proliferative epithelium, abnormal ductal branching, enlarged terminal end buds [94]. Reduced Stat5 activation and β-casein expression upon lactogenic stimulation in primary mammary epithelial cells [124].	NR	NR
Kidney	Thickening of glomerular basement membrane, focal loss of split diaphragms, proteinuria [125]. Reduced adhesion of primary mesangial cells to ECM, increased mesangial proliferation due to increased MAPK activity [126].	NR	NR
Vascular System	Reduced neointimal thickening after vascular injury [30]. Reduced adhesion and migration to collagen I and MMP secretion by smooth muscle (SM) cells [147]. Reduced atherosclerotic calcifications in Ldlr−/− background [177]. Increased matrix secretion, proliferation and migration of vessel wall SM cells[135].	No effect on adhesion, migration, or proliferation of vascular SM cells [152].	NR
Inflammatory/Fibrotic response/Immune system function	Reduced inflammatory response to LPS, reduced glomerular fibrosis and inflammation in hypertension [178]. Impaired macrophage migration and invasion in response to MCP-1 [157,150]. Reduced inflammatory and fibrotic response to bleomycin-induced lung injury, no p-38 MAPK activation [179]. Reduced macrophage recruitment, inflammation, and fibrosis in atherogenesis in Ldlr−/− background [180]. Reduced proinflammatory and profibrotic cells in kidney in hereditary collagen IV disease (COL4A3−/− background) [181]. Reduced inflammation and fibrosis in obstructed kidneys [157].	Increased inflammatory and proliferative response of hepatic stellate cells and macrophages to chronic liver injury [129].	NR
Skin	NR	Reduced proliferation, invasion through basement membrane and MMP activity of dermal fibroblasts [128]. Impaired dermal wound healing due to defective ECM remodeling by skin fibroblasts [55].	NR
Ear	Unable to control ear movement [94]. Loss of auditory function and profound structural changes throughout the cochlear duct [127].	NR	NR
Reproduction	Impaired blastocyst implantation into uterine wall [94].	NR	Mouse: Impaired spermatogenesis [121,123] and ovulation [121,122] in slie mice.
Susceptibility/Resistance to diseases	Resistant to bleomycin-induced lung fibrosis [179]. Resistant to hypertension-induced renal failure [178]. Decreased atherosclerosis in Ldlr−/− background [180,177]. Delayed renal fibrosis, inflammation, and death in hereditary collagen IV disease (COL4A3 background) [181].	Increased susceptibility of hepatic tissue to colon carcinoma metastasis [130]. Increased susceptibility to hepatic fibrosis in chronic liver injury [129].	NR

NR: Not reported