ArticleThe Journal of clinical investigation2012
Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
279 citing papers in PubMed, 1 synthesis or guideline pooled it, 442 citations in OpenAlex.
- Therapeutic Potential of Ketogenic Interventions for Autosomal-Dominant Polycystic Kidney Disease: A Systematic Review.Nutrients · 2024Pooled it
- Pirfenidone treatment attenuates fibrosis in autosomal dominant polycystic kidney disease.JCI insight · 2026Article
- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- Article
- Dysregulated ferritin and iron homeostasis in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2026Article
- Targeting Runx1 Slows Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- Combination siRNA delivery as a therapeutic strategy for ADPKD.bioRxiv : the preprint server for biology · 2026Article
- Myofibroblast- specific autophagy drives cyst growth in autosomal dominant polycystic kidney disease.Cell communication and signaling : CCS · 2026Article
- Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel.Nature communications · 2026Article
- Review
- Collecting Duct-Targeted Lipid Nanoparticles DeliverbioRxiv : the preprint server for biology · 2026Article
- Article
- Kidney Volume and Molecular Processes are Dynamic in ADPKD.Kidney international reports · 2026Article
- The Renal Micro-RNA Expression Profile of Pkd1RC/RC Mice Changes Longitudinally with the Progression of the Disease.Kidney360 · 2026Article
- Regulation of the PKD2 channel function and associated disease phenotypes by RASSF4.Communications biology · 2026Article
- GV-001, An Oral Available Histone Deacetylase 6 Inhibitor for the Treatment of Autosomal Dominant Polycystic Kidney Disease.Journal of medicinal chemistry · 2026Article
- Designing genome editing experiments with EditABLE.Genome biology · 2026Article
- A Ciliary Phosphoinositide Pathway Regulates the Dosage of Polycystins in Primary Cilia.Journal of the American Society of Nephrology : JASN · 2026Article
- TLR2 Activation Enhances Inflammatory Signaling and Accelerates Cyst Growth and Renal Fibrosis in Polycystic Kidney Disease Mice.International journal of molecular sciences · 2026Article
219 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations to PKD1 or PKD2, triggering progressive cystogenesis and typically leading to end-stage renal disease in midlife. The phenotypic spectrum, however, ranges from in utero onset to adequate renal function at old age. Recent patient data suggest that the disease is dosage dependent, where incompletely penetrant alleles influence disease severity. Here, we have developed a knockin mouse model matching a likely disease variant, PKD1 p.R3277C (RC), and have proved that its functionally hypomorphic nature modifies the ADPKD phenotype. While Pkd1+/null mice are normal, Pkd1RC/null mice have rapidly progressive disease, and Pkd1RC/RC animals develop gradual cystogenesis. These models effectively mimic the pathophysiological features of in utero-onset and typical ADPKD, respectively, correlating the level of functional Pkd1 product with disease severity, highlighting the dosage dependence of cystogenesis. Additionally, molecular analyses identified p.R3277C as a temperature-sensitive folding/trafficking mutant, and length defects in collecting duct primary cilia, the organelle central to PKD pathogenesis, were clearly detected for the first time to our knowledge in PKD1. Altogether, this study highlights the role that in trans variants at the disease locus can play in phenotypic modification of dominant diseases and provides a truly orthologous PKD1 model, optimal for therapeutic testing.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.