Polycystic kidney disease
Genetic model
Spontaneous genetic trait model
Transgenic model
Knock-out model
Surgical model
Renal ablation model
Agent-induced model
Metabolic model of nephropathy
Diabetic nephropathy model
Type 1 diabetes associated diabetic nephropathy model
Streptozotocin-induced model of diabetic nephropathy
Streptozotocin (STZ) is an analogue of N-acetylglucosamine (GlcNAc). It is readily transported into pancreatic beta-cells by GLUT-2 and selectively inhibits the activity of beta-cell O-GlcNAcase, which is responsible for removing O-GlcNAc from protein. This causes irreversible O-glycosylation of intracellular proteins and results in beta-cell apoptosis. STZ can be used to study diabetic nephropathy in most rodent strains. However the severity of injury is dependent on genetic background. Moreover, GLUT-2 is also expressed by renal and hepatic cells. The cytotoxicity of STZ is thus not restricted to pancreatic beta-cells but also affects kidney and liver cells.
diabetic nephropathy induced by streptozotocin
Streptozotocin-induced mouse model of diabetic nephropathy
Low dose streptozotocin-induced model of diabetic nephropathy
Multiple low-dose injection of STZ (50-55mg/kg for 5 consecutive days, i.p.). C57BLKS and DBA2/J mouse strains are more susceptible to low-dose STZ-induced diabetic nephropathy compared to C57Bl/6, FVB/N, A/J, BALB/C or Swiss Webster genetic backgrounds.
low-dose mouse model of diabetic nephropathy
High dose streptozotocin-induced model of diabetic nephropathy
Single high-dose injection of STZ (>= 200mg/kg, i.p.) or two-dose regimen (2x100-125mg/kg for 2 consecutive days, i.p.).
high-dose mouse model of diabetic nephropathy
Streptozotocin-induced model of diabetic nephropathy associated with eNOS deletion
Decreased eNOS activity is associated with the development of advanced nephropathy in patients with type 1 and type 2 diabetes.
Low dose streptozotocin-induced model of diabetic nephropathy associated with eNOS deletion
This model has been developed in the nephropathy resistant C57Bl/6 background. Compared with diabetic WT mice, low dose-STZ eNOS(-/-) mice develop more severe albuminuria, mesangial expansion, mesangiolysis and focal sclerosis.
High dose streptozotocin-induced model of diabetic nephropathy associated with eNOS deletion
This model has been developed in the nephropathy resistant C57Bl/6 background. Compared with diabetic WT mice, high dose-STZ eNOS(-/-) mice develop more severe albuminuria, mesangial expansion, mesangiolysis and focal sclerosis. Diabetic knock-out mice also exhibit robust glomerulosclerosis and tubulointerstitial injury, and significant hypertension and mortality.
Streptozotocin-induced rat model of diabetic nephropathy
STZ-induced diabetic nephropathy is commonly studied in Sprague-Dawley (SD), Wistar-Kyoto (WKY), or spontaneously hypertensive (SHR) rats (SD=55mg/kg, WKY=60mg/kg, SHR=45mg/kg, one injection, i.v.).
Streptozotocin-induced rat model of diabetic nephropathy associated with uninephrectomy
Uninephrectomy is thought to accelerate the progression of renal injury. However, interpretation of this model is complex as it is difficult to dissociate the relative contribution of STZ-induced hyperglycemia and uninephrectomy-induced changes in the development of glomerular lesions.
Akita model of diabetic nephropathy
Autosomal dominant mutation, generally studied in heterozygous state. Lead to impaired beta cell function and survival due to insulin misfolding and endoplasmic reticular stress. DBA2/J mouse strain is more susceptible to Akita mutation compared to C57Bl/6 and FVB/N genetic backgrounds.
Akita model of diabetic nephropathy associated with eNOS deletion
FVB-OVE26
FVB(Cg)-Tg(Ins2-CALM1)26Ove Tg(Cryaa-TAg)1Ove/PneJ
Transgenic model of early-onset type 1 diabetes. Generated in FVB/N background. The calmodulin gene is under the control of a rat insulin 2 promoter. Calmodulin is thus specifically overexpressed in the beta cells and exerts beta-cell toxicity. CaMTg mice develop persistent proteinuria, tubulointerstital fibrosis, glomerualr basement thickening and a considerable increase in the glomerular and mesangial areas. Moreover, these mice exhibit most of the pathologic hallmarks of human diabetic nephropathy, that is mesangiolysis, Kimmelstiel-Wilson-like nodular lesions, exudative lesions and arteriolar hyalinosis.
NOD model of diabetic nephropathy
The susceptibility to type 1 diabetes in NOD mice is polygenic and strongly depends on environment. Diabetes develop as a result of leukocytic infiltrate of pancreatic islet (auto-immune disease). However, the onset of diabetes is very variable, as the incidence of spontaneous diabetes in the NOD mouse is 60-80% in females, but dramatically lower in males (20-30%). Female NOD mice exhibit increased glomerular area, glomerulosclerosis and glomerular basal membrane thickness at 50 weeks of age.
Type 2 diabetes associated diabetic nephropathy model
db/db model of diabetic nephropathy
C57BKS(db/db) is one of the best model of nephropathy associated with type 2 diabetes. The db/db mouse, resulting from a mutation in the leptin receptor gene (Lpr), develops hyperglycaemia, glomerular hypertrophy, and sclerosis with age but is not associated with lesions of tubulointerstitial fibrosis. Mutations of the leptin receptor are however a rare cause of type 2 diabetes in humans, and the direct relevance to the human condition may thus be argued.
db/db model of diabetic nephropathy associated wih eNOS deletion
Decreased eNOS activity is associated with the development of advanced nephropathy in patients with type 1 and type 2 diabetes. This model has been developed in C57BLKS background. Compared to eNOS(+/+) mice, eNOS(-/-) mice exhibit greater mesangial expansion, glomerular basement membrane thickening, arteriolar hyalinosis, mesangiolysis, nodular glomerulosclerosis and tubulointerstitial injury.
Zucker model of diabetic nephropathy
Obese Zucker Diabetic Fatty (ZDF) rats are homozygotes for a mutation in the leptin receptor gene (Lpr), thus reducing the affinity of the leptin receptor for its ligand. Male obese ZDF rats are glucose-intolerant, transiently hyperinsulinemic, hyperlipidemic, hyperleptinemic and develop mild nephropathy. Female obese ZDF rats do not express the diabetic phenotype only on diabetogenic diet, not on regular chow diet. Lean ZDF rats, whether male or female do not express the diabetic phenotype.
NONcNZO10/LtJ model of diabetic nephropathy
NONcNZO10/LtJ is an inbred congenic strain derived from cross between the NonObese Nondiabetic (NON/LtJ) strain and the New Zealand Obese (NZO/HlLt) strain. These mice have been developed as a polygenic model of obesity-induced type 2 diabetes and metabolic syndrome. The obesity is more moderate than in the db/db strain.
KKAy model of diabetic nephropathy
The KKAy mouse is a congenital strain established by transduction of yellow obese gene (Ay) into the KK mice. The inbred KK mice develops type 2 diabetes with moderate obesity and hyperglycemia. The introduction of the Ay allele causes massive obesity and overt type 2 diabetes with elevated plasma glucose and insulin resistance. Furthermore, KKAy mice exhibits albuminuria, mesangial expansion, glomerulosclerosis and glomerular capillary basement thickening.
Ureteral obstruction model
Ureteral obstruction model, Adult
Partial ureteral obstruction model, Adult
Partial unilateral ureteral obstruction model, Adult
Partial bilateral ureteral obstruction model, Adult
Complete ureteral obstruction model, Adult
Complete unilateral obstruction model, Adult
Complete bilateral obstruction model, Adult
Ureteral obstruction model, Fetal
Partial ureteral obstruction model, Fetal
Partial unilateral ureteral obstruction model, Fetal
Partial bilateral ureteral obstruction model, Fetal
Complete ureteral obstruction model, Fetal
Complete unilateral obstruction model, Fetal
Complete bilateral obstruction model, Fetal
Ureteral obstruction model, Neonatal
Partial ureteral obstruction model, Neonatal
Partial unilateral ureteral obstruction model, Neonatal
Partial bilateral ureteral obstruction model, Neonatal
Complete ureteral obstruction model, Neonatal
Complete unilateral obstruction model, Neonatal
Complete bilateral obstruction model, Neonatal
Chronic renal failure model
Sub-total nephrectomy model
Rather that mimicking a renal disease, sub-total nephrectomy models the progressive renal failure associated to loss of renal mass. The rate of progression to renal failure is closely related to the amount of tissue excised. It is thus necessary to weight and calculate the proportion of excised tissue to limit inter-individual variations.
Sub-total nephrectomy ablation model
In this model, one kidney is removed (uninephrectomy) and blood flow is interrupted to the poles of the remaining kidney (ligation of polar branches of the renal artery). This ligation model is associated with severe hypertension.
Sub-total nephrectomy ligation model
In this model, one kidney is removed and the 2 poles of the remaining kidney are removed 1-2 weeks later.
Acute renal failure model
Ischemia/reperfusion injury model
Ischemia/reperfusion is the major cause of AKI in native and transplant kidneys. The consequences of ischemia/reperfusion are proportional to the period of ischemia, and depends on animal species and age.
Bilateral ischemia/reperfusion injury model
Bilateral clamping of the renal pedicele. Simulates AKI induced by severe acute hypotension.
Unilateral ischemia/reperfusion injury model
Unilateral clamping of the renal pedicele. Allows comparison with contralateral kidney and increases survival rate.
Unilateral ischemia/reperfusion injury model associated with uninephrectomy
Uninephrectomy is followed by unilateral clamping of the pedicele of the remaining kidney. More closely mimicks the situation occuring in renal transplantation.
Nephrotoxic model
Kidneys are particularly prone to toxic damages, due to their ability to concentrate and metabolize chemicals. Molecules can be toxic for either renal vasculature, glomerular cells, and tubular epithelium. Most often, in animal models mimicking the nephrotoxic insults, single exposure results in acute renal disease with resolution and regeneration whereas repeat exposures induces progressive renal disease.
Podocyte-toxicity model
Focal segmental glomerulosclerosis model
Primary focal segmental glomerulosclerosis model
Toxic model of focal segmental glomerulosclerosis
Toxic models induce direct podocyte injury including podocyte oxidative stress, foot process effacement and glomerulosclerosis.
Secondary focal segmental glomerulosclerosis model
Post adaptative focal segmental glomerulosclerosis
Renal ablation models induce glomerular hypertension (elevated glomerular capillary pressures and flow rates) as a consequence of the reduced number of functioning nephrons or other glomerular stress. This adaptative response is considered as the cause of secondary podocyte injury
Nephrotic syndrome model
Adriamycin-induced nephrotic syndrome model
Adriamycin is an antibiotic with antineoplasic properties (DNA replication inhibition). Its use is associated with nephrotic syndrome in clinic. The principal site of action of adriamycin is the podocyte (foot process fusion).
Puromycin aminonucleoside-induced nephrotic syndrome model
PAN is an antibiotic with antineoplasic properties. Its use is associated with nephrotic syndrome in clinic. The principal site of action of PAN is the podocyte (foot process fusion). Mice are not susceptible to PAN.
Tubular-toxicity model
Cisplatin-induced nephropathy model
Cisplatin is an anti-tumor agent. It is absorbed and accumulated in the S3 segment of the proximal tubule, inducing apoptosis and necrosis of epithelial cells. Cisplatin-induced nephropathy is now considered to be more a generic model than a model mimicking the clinical situation as its use declines in clinic.
Mercuric chloride-induced nephropathy model
Gentamicin-induced nephropathy model
Gentaminin is a aminoglycoside antibiotic. Proximal tubule concentrate aminoglycoside, inducing mitochondrial and lysosomal dysfunction. This model is highly relevant clinically. It displays myeloid bodies in proximal cells as it is observed in humans.
Folic acid-induced nephropathy model
Ciclosporin-induced nephropathy model
Immune-mediated model
Glomerulonephritis model
Mesangioproliferative glomerulonephritis model
Mesangial proliferative glomerulonephritis model
Thy-1 nephritis model
Thy-1 (THYmocyte differentiation antigen 1), also known as CD90, is a 25-37 kDa cell surface protein originally found to be expressed on thymocytes.
Thy-1 nephritis rat model
Rats express the Thy-1.1 antigen on mesangial cells. To induce Thy-1 nephritis, rats are injected with a rabbit anti-thymocyte serum (ATS) or a mouse anti-Thy 1 mAB (e.g. OX-7 or 1-22-3). Thy-1 nephritis is characterized by initial mesangolysis, followed by mesangial proliferation and mesangial matrix expansion, similar to that seen in human variants of mesangial proliferative glomerulonephritis. However, in the rat model w/o uninephrectomy, mesangial proliferation is transient and spontaneous regeneration occurs (reversible model).
Thy-1 nephritis rat model associated with uninephrectomy
Rats express the Thy-1.1 antigen on mesangial cells. To induce Thy-1 nephritis, rats are injected with a rabbit anti-thymocyte serum (ATS) or a mouse anti-Thy 1 mAB (e.g. OX-7 or 1-22-3). Thy-1 nephritis is characterized by initial mesangolysis, followed by mesangial proliferation and mesangial matrix expansion, similar to that seen in human variants of mesangial proliferative glomerulonephritis. In the rat model associated with uninephrectomy, progressive development of glomerulosclerosis occurs (irreversible model), perharps mimicking more closely what happen during mesangial proliferative glomerulonephritis in humans.
Thy-1 nephritis mouse model
Normal mice do not express the Thy-1.1 antigen in the kidney. For this reason, transgenic mice that ectopically express a mice-human chimeric Thy-1.1 antigen on podocytes have been developed. These mice slowly and spontaneously develop albuminuria and focal segmental glomerulosclerosis (FSGS). Injection of mAb directed against the Thy-1.1 antigen or against aminopeptidase (APA, an enzyme expressed in proximal tubule epithelial cells and podocytes), induces an acute albuminuria within 1 day and accelerate the development of FSGS lesions within 3 wk. FSGS lesions in this mouse model mimicks the collapsing variant of human FSGS.
Anti-GBM nephritis model
Habu snake venom model
Intravenous injection of HSV provokes acute focal mesangial proliferative glomerulonephritis in rodents.
Membranoproliferative glomerulonephritis model
MPGN is characterized by glomerular hypercellularity, mesangial matrix expansion, thickening of the peripheral capillary walls, progressive loss of renal function eventually resulting in end-stage renal disease. Clinically, MPGN is characterized by proteinuria (up to nephrotic range), hypertension, and haematuria.
CFH-deficiency model
CFH-deficiency mouse model
MPGN II/DDD (dense deposit disease) similarities: mesangial hypercellularity, mesangial matrix expansion, capillary wall thickening and electron-dense deposits (C3 and C9) in the subendothelial space but not in the GBM. Cfh(-/-) mice also develop proteinuria, haematuria and die from renal failure.
CFH-deficiency piglet model
MPGN II/DDD (dense deposit disease) phenotype: glomerular hypercellularity, mesangial matrix expansion, electron-dense material and C3 deposits within GBM. Animals die from renal failure.
Calcium oxalate monohydrate in vitro model
Interstitial fibrosis and tubular atrophy model
Interstitial fibrosis and tubular atrophy model (allogenic transplantation)
Acute renal allograft rejection model (allogenic transplantation)
Hypoxia in vitro model
Oxidative stress in vitro model
H2O2 in vitro model
PDGF in vitro model
CTGF in vitro model
TGFbeta in vitro model
Immunosuppressor in vitro model
Sirolimus in vitro model
Tacrolimus in vitro model
Vasopressine in vitro model
Nephrotoxicant in vitro model
Cisplatin in vitro model
Gentamicin in vitro model
LPS induced in vitro model
LPS induced model
Immunosuppressor-induced nephropathy model
Cystic kidney disease model
Polycystic kidney disease model
AGE in vitro model
Lupus nephritis model
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus (SLE), a disease of the immune system. About half of cases of SLE demonstrate signs of lupus nephritis at one time or another. Renal-specific signs include proteinuria (100%), nephrotic syndrome (55%), granular casts (30%), red cell casts (10%), microhematuria (80%), macrohematuria (2%), reduced renal function (60%), RPGN (30%), ARF (2%), hypertension (35%), hyperkalemia (15%) and tubular abnormalities (70%).
Aristolochic acids are a family of carcinogenic, mutagenic, and nephrotoxic compounds commonly found in the Aristolochiaceae family of plants, including Aristolochia and Asarum (wild ginger), which are commonly used in Chinese herbal medicine. Aristolochic acids are hypothesized to be causative agents in Balkan endemic nephropathy; and a related—possibly identical—condition known as "Chinese herbs nephropathy".
Develomental cigarette smoke-nephrotoxic model
Foetal exposure to cigarette smoke during pregancy (developmental cigarette smoke exposure (CSE)) results in intrauterine growth retardation with a predisposition to obesity and cardiovascular disease at maturity.
The term diffuse mesangial sclerosis (DMS) indicates a characteristic glomerular histological alteration that occurs in childhood nephrotic syndrome and is associated with genetic alterations. Histopathological findings consist in glomeruli with mesangial expansion by increased mesangial matrix, with capillary walls that may be normal initially, but with hypertrophy and hyperplasia of podocytes. By advancing the process (usually in months or a few years), there is progressively greater mesangial expansion, capillary lumens are lost and the capillary walls are difficult to see clearly. In the terminal stages there is glomerular sclerosis.
A rare congenital syndrome caused by mutations in the WT1 gene. Causes kidney failure before age 3, abnormal development of the sexual organs, and, in most cases, Wilms tumor (a type of kidney cancer). Children with Denys-Drash syndrome are also at high risk of some other types of cancer.
HIV-associated nephropathy (HIVAN) refers to kidney disease developing in association with HIV infection. The most common, or "classical", type of HIV-associated nephropathy is a collapsing focal segmental glomerulosclerosis (FSGS), though other forms of kidney disease may also occur with HIV. HIVAN may be caused by direct infection of the renal cells with the HIV-1 virus, with resulting renal damage through the viral gene products. It could also be caused by changes in the release of cytokines during HIV infection.