Disease relevance of Pkdr1_mapped

• Autosomal dominant polycystic kidney disease (PKD) is the most common genetic disease that leads to kidney failure in humans [1].
• Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease [2].
• Characterization of a major modifier locus for polycystic kidney disease (Modpkdr1) in the Han:SPRD(cy/+) rat in a region conserved with a mouse modifier locus for Alport syndrome [3].
• Caroli's disease (congenital intrahepatic biliary dilatation) associated with congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease [4].
• Hereditary polycystic kidney disease. Adult polycystic kidney disease associated with renal hypertension, renal osteodystrophy, and uremic enteritis in SPRD rats [5].

Psychiatry related information on Pkdr1_mapped

• The Han:SPRD-cy rat model of polycystic kidney disease (PKD) features prominent renal interstitial inflammation and fibrosis that is amenable to dietary modification [6].

High impact information on Pkdr1_mapped

• Defective planar cell polarity in polycystic kidney disease [7].
• Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene [8].
• BACKGROUND & AIMS: Recent studies have showed that proteins associated with polycystic kidney disease (PKD) are expressed in cilia, linking this organelle and cyst formation in the kidney, but involvement of cilia in PKD-related biliary cystogenesis has not been shown [9].
• Cy/+ rats with PKD have kidney failure as indicated by a significant increase in blood urea nitrogen [2].
• In summary, in a rat model of PKD, caspase inhibition with IDN-8050 (i) decreases apoptosis and proliferation in cystic and noncystic tubules; (ii) inhibits renal enlargement and cystogenesis, and (iii) attenuates the loss of kidney function [2].

Chemical compound and disease context of Pkdr1_mapped

• These results support the importance of cAMP in the pathogenesis of polycystic kidney disease, confirm the effectiveness of a VPV2 antagonist to be used in clinical trials for this disease, and suggest that OPC-31260 and OPC-41061 inhibit Ras/mitogen-activated protein kinase signaling in polycystic kidneys [10].
• METHODS: To determine whether the inhibition of EGFR tyrosine kinase activity can attenuate the development of PKD in the Han:SPRD rat, a frequently used animal model of autosomal-dominant slowly progressive PKD (ADPKD), wild-type and cy/+ rats were treated with EKI-785 or EKB-569 or with vehicle alone [11].
• To explore the hypothesis that RAS adaptations contribute to disease progression, we examined RAS activity and the long-term consequences of antihypertensive drugs, which suppress (enalapril) or stimulate (hydralazine) the RAS, in experimental polycystic kidney disease [12].
• To determine whether amelioration of interstitial inflammation and fibrosis may diminish cyst expansion/kidney enlargement and stabilize renal function, we administered methylprednisolone, an anti-inflammatory drug with antifibrogenic effects, to mice and rats with hereditary polycystic kidney disease [13].
• We undertook a morphometric and proton nuclear magnetic resonance ((1)H-NMR) study to test the hypothesis that 1% dietary betaine supplementation would ameliorate renal disease in the heterozygous Han:SPRD-cy rat, a model of polycystic kidney disease (PKD) and progressive chronic renal failure [14].

Biological context of Pkdr1_mapped

• Missense mutation in sterile alpha motif of novel protein SamCystin is associated with polycystic kidney disease in (cy/+) rat [1].
• The genetic dissection of PKD in the cross allowed us to detect a modifier locus, Modpkdr1, on rat chromosome 8 that controls PKD severity, kidney mass and plasma urea concentration [3].
• Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease [15].
• Comparative genome mapping also provided an inventory of potential candidate genes for modifier(s) of PKD [3].
• We report here the complete nucleotide sequence of Ke 6a cDNA and the expression of the Ke 6 gene in murine models of PKD [15].

Anatomical context of Pkdr1_mapped

• Alterations in basement membrane components, notably proteoglycans, in a rat model of polycystic kidney disease have been investigated [16].
• Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well [17].
• The presence of cathepsins could be demonstrated in cyst fluid from homozygous PKD rats and urinary excretion of cathepsins was enhanced in heterozygous animals [18].
• The decrease in cathepsins in PKD was specific for tubules, as enzyme activities in glomeruli and liver tissue were unchanged and limited to the lysosomal compartment, since marker enzymes for cytoplasm, endoplasmatic reticulum and mitochondria were all normal [18].
• However, it has long been known that the photoreceptor-bearing outer segments of retinal rods and cones are modified primary cilia and it has recently been found that kidney cells' primary cilia are sensitive flowmeters the disabling of which causes polycystic kidney disease [19].

Associations of Pkdr1_mapped with chemical compounds

• This article reports the positional cloning and mutation analysis of the rat PKD gene, which revealed a C to T transition that replaces an arginine by a tryptophan at amino acid 823 in the protein sequence [1].
• Basement membrane chondroitin sulfate proteoglycan alterations in a rat model of polycystic kidney disease [16].
• This study determined whether ingestion of potassium citrate and citric acid would ameliorate PKD [20].
• Healthy normal and heterozygous littermate Han:SPRD rats with autosomal dominant PKD were provided with either tap water or 55 mM K3citrate/67 mM citric acid solution (KCitr) to drink starting at the age of 1 mo [20].
• The administration of ammonium chloride or of sodium or potassium bicarbonate has marked effects on the development of polycystic kidney disease (PKD) in Han:SPRD rats [21].

Regulatory relationships of Pkdr1_mapped

• In conclusion, a marked, yet reversible induction of clusterin occurred in chemically induced polycystic kidney disease [22].
• BACKGROUND: Increasing evidence supports an important role for the epidermal growth factor (EGF)/transforming growth factor-alpha (TGF-alpha)/EGF receptor (EGFR) axis in promoting tubular epithelial cell proliferation and cyst formation in polycystic kidney disease (PKD) [11].

Other interactions of Pkdr1_mapped

• Tubular gelatinase A (MMP-2) and its tissue inhibitors in polycystic kidney disease in the Han:SPRD rat [23].
• BACKGROUND: Mutations in PKD2 account for 15% of patients with autosomal dominant polycystic kidney disease [24].
• Androgen receptor pathway in rats with autosomal dominant polycystic kidney disease [25].
• The B1 receptor antagonist had no influence on functional renal parameters.CONCLUSIONS: The present study demonstrates an age-dependent activation of the renal KKS in rats with polycystic kidney disease [26].
• PKD1 is responsible for most cases of autosomal dominant polycystic kidney disease, which has been described as "neoplasia in disguise." Polycystin-1 is a membrane protein localized to adherens junctions in a complex containing E-cadherin and alpha-, beta-, and gamma-catenins [27].

Analytical, diagnostic and therapeutic context of Pkdr1_mapped

• Accelerated renal death after unilateral nephrectomy in a rat strain suffering from autosomal dominant polycystic kidney disease [28].
• Gene therapy has the potential to provide a therapeutic strategy for numerous renal diseases such as diabetic nephropathy, chronic rejection, Alport syndrome, polycystic kidney disease, and inherited tubular disorders [29].
• Recently an animal model of autosomal dominant PKD in the rat became available allowing this topic to be studied [30].
• ELISA determinations revealed increased expression of interstitial collagens type-I, -V and -VI in PKD vs control and they remained elevated following recovery, while that of type-III was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)[31]
• The Han:SPRD rat model for inherited polycystic kidney disease (PKD) was characterized (clinical parameters, morphology, immunohistochemistry and in situ hybridization) [32].

References