|Genetic Model||Category||Specific Features||Site of Fibrosis|
|Tight skin 1 mouse models(Tsk1/+)||Models with spontaneous mutations||
- They are bred as heterozygotes because of lethal homozygous mutation.|
- They have thickened skin which is tightly joined to the subcutaneous tissue.
- The deposition of elastin has risen but there isn’t elasticity in the skin.
- They present an emphysema-like pathology in the lung due to the increased elastin.
- They have an enlarged heart and skeleton.
- There is partial duplication of the fibrillin-1 gene as a mutation on chromosome 2 which seems to suppress raised levels of TGFβ in the extracellular matrix and following stimulating collagen synthesis.
|Tight skin 2 mouse models (Tsk2/+)||Models with spontaneous mutations||
- They are generated via mutagenic agent ethylnitrosourea.|
- Tight skin can be found in the interscapular region.
- The mutation is placed on chromosome 1.
- They can mimic many characteristics of systemic sclerosis subjects, containing increased deposition of the dermal extracellular matrix, tight skin, and autoantibodies.
- They present enhanced transcription percentages of dermal fibroblasts type I and III collagen.
- Increased autoimmunity have reported in Tsk2/+ models.
|UCD-200 chickens||Models with spontaneous mutations||
- They are identified by infiltration of perivascular lymphocytic, vascular occlusion caused by endothelial injuries, fibrosis of the skin and visceral organs, and spotted antinuclear antibodies.|
- There is a genetic defect with an autosomal recessive mode of inheritance or multiple loci interactions.
- Five genes including which have been reported to have importance in the pathology of systemic sclerosis including (TGFBR1, IGFBP3, EXOC2/IRF4, CCR8 (located on chromosome 2), and SOCS1(located at chromosome 14) have been recognized to present a high association with the disease.
- Mutation of COL1A2 gene (located on chromosome 2) may play a role in avian systemic sclerosis.
|Skin and Visceral organs|
|Endothelin-1 mouse models||Transgenic models of fibrosis||
- There is increased expression of endothelin-1.|
- They have endothelial dysfunction.
- They develop glomerulosclerosis and interstitial fibrosis.
|Kidney and Lung|
|Fos-related antigen-2 mouse models||Transgenic models of fibrosis||
- There is overexpressing the Fos-related antigen-2 (FRA-2)|
- They show microangiopathy along with progression of skin fibrosis.
|Skin and Lung|
|Type I TGFβ receptor transgenic models||Transgenic models of fibrosis||
- There is upregulating of the type I TGFβ receptor in fibroblasts on a Cre-ER transgenic background.|
- There are increasing levels of collagen deposition in the skin of through the aging.
|Kinase-deficient type II TGFβ receptor transgenic models||Transgenic models of fibrosis||
- There is a fibroblast-specific transcriptional enhancer (applied to specifically express a kinase-deficient mutant type II TGFβ receptor which can involve TGFβ) upstream of the COL1A2 collagen gene.|
- There is the lack of immune activation and autoantibodies.
|Skin and Lung|
|PDGF receptor-α transgenic models of fibrosis||Transgenic models of fibrosis||- There is conditionally expressed PDGF receptor-α activating mutations.||Skin and Internal organs|
|Caveolin-1 deficient models||Knockout models of fibrosis||
- There are raised collagen and fibronectin accumulation along with increased amounts of myofibroblasts.|
- There is oxidative stress condition.
|Early growth response protein-1 knockout mouse models||Knockout models of fibrosis||- There are reduced amounts of infiltrating inflammatory cells in the skin along with the reduced dermal thickness and expression of collagen.||Skin and Lung|
|Friend leukemia integration factor-1 conditional knockout mouse models||Knockout models of fibrosis||
- There is risen vascular permeability.|
- They mimic the collagen fibril formation abnormalities in systemic sclerosis.
|Macrophage chemoattractant protein-1 mouse models||Knockout models of fibrosis||
- There are reduced fibrotic replies after the injection of basic fibroblast growth factor and connective tissue growth factor into the skin.|
- There are fewer mast cells, reduction of macrophage recruitment, and fewer CD4+ T-cell amounts.
|Microsomal prostaglandin E2 synthase-1 knockout models||Knockout models of fibrosis||- There are bleomycin-induced fibrosis resistant, α-smooth muscle actin levels reduction, and macrophages numbers reduction.||Skin and Lung|
|Peroxisome proliferator-activated receptor-gamma deficient models||Knockout models of fibrosis||
- There is more extensive skin thickening with bleomycin compared to wild-type.|
- They can help to determine the function of this protein in collagen synthesis.
|PTEN conditional knockout mouse models||Knockout models of fibrosis||- There are developed thickened skin and collagen deposition along with raised α-smooth muscle actin-bearing fibroblasts numbers, connective tissue growth factor-positive fibroblasts, and proliferating cell nuclear antigen-positive fibroblasts.||Skin|
|Relaxin knockout mouse models||Knockout models of fibrosis||- There is developed skin collagen deposition over time.||Skin|