ArticlePhysiological reports2016
Differences in the timing and magnitude of Pkd1 gene deletion determine the severity of polycystic kidney disease in an orthologous mouse model of ADPKD.
Article in Physiological reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- GLPG2737, a CFTR Inhibitor, Prevents Cyst Growth in Preclinical Models of Autosomal Dominant Polycystic Kidney Disease.American journal of nephrology · 2025Article
- Aberrant centrosome biogenesis disrupts nephron and collecting duct progenitor growth and fate resulting in fibrocystic kidney disease.Development (Cambridge, England) · 2023Article
- ModelingMolecular therapy. Methods & clinical development · 2023Article
- Glucosylceramide synthase inhibition protects against cardiac hypertrophy in chronic kidney disease.Scientific reports · 2022Article
- Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD.Frontiers in molecular biosciences · 2022Review
- Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidneys of three Pkd1-deficient mouse models.Scientific reports · 2021Article
- Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases.Frontiers in physiology · 2021Review
- CystAnalyser: A new software tool for the automatic detection and quantification of cysts in Polycystic Kidney and Liver Disease, and other cystic disorders.PLoS computational biology · 2020Article
- Correction of cilia structure and function alleviates multi-organ pathology in Bardet-Biedl syndrome mice.Human molecular genetics · 2020Article
- Hyperactivity of Mek in TNS1 knockouts leads to potential treatments for cystic kidney diseases.Cell death & disease · 2019Article
- Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.Clinical kidney journal · 2018Review
- Polycystic kidney features of the renal pathology in glycogen storage disease type I: possible evolution to renal neoplasia.Journal of inherited metabolic disease · 2018Review
- Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth inJournal of the American Society of Nephrology : JASN · 2018Article
- Differences in the timing and magnitude of Pkd1 gene deletion determine the severity of polycystic kidney disease in an orthologous mouse model of ADPKD.Physiological reports · 2016Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
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Abstract
Development of a disease-modifying therapy to treat autosomal dominant polycystic kidney disease (ADPKD) requires well-characterized preclinical models that accurately reflect the pathology and biochemical changes associated with the disease. Using a Pkd1 conditional knockout mouse, we demonstrate that subtly altering the timing and extent of Pkd1 deletion can have a significant impact on the origin and severity of kidney cyst formation. Pkd1 deletion on postnatal day 1 or 2 results in cysts arising from both the cortical and medullary regions, whereas deletion on postnatal days 3-8 results in primarily medullary cyst formation. Altering the extent of Pkd1 deletion by modulating the tamoxifen dose produces dose-dependent changes in the severity, but not origin, of cystogenesis. Limited Pkd1 deletion produces progressive kidney cystogenesis, accompanied by interstitial fibrosis and loss of kidney function. Cyst growth occurs in two phases: an early, rapid growth phase, followed by a later, slow growth period. Analysis of biochemical pathway changes in cystic kidneys reveals dysregulation of the cell cycle, increased proliferation and apoptosis, activation of Mek-Erk, Akt-mTOR, and Wnt-β-catenin signaling pathways, and altered glycosphingolipid metabolism that resemble the biochemical changes occurring in human ADPKD kidneys. These pathways are normally active in neonatal mouse kidneys until repressed around 3 weeks of age; however, they remain active following Pkd1 deletion. Together, this work describes the key parameters to accurately model the pathological and biochemical changes associated with ADPKD in a conditional mouse model.
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