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Updated: Aug 30, 2026
Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
Murine models of polycystic kidney disease: molecular and therapeutic insights
1Division of Genetic and Translational Medicine, Department of Medicine, University of Alabama at Birmingham, Kaul 740, 1530 3rd Ave. South 19th St., Birmingham, AL 35294, USA. lgw@uab.edu
Abstract:
Numerous murine (mouse and rat) models of polycystic kidney disease (PKD) have been described in which the mutant phenotype results from a spontaneous mutation or engineering via chemical mutagenesis, transgenic technologies, or gene-specific targeting in mouse orthologs of human PKD genes. These murine phenotypes closely resemble human PKD, with common abnormalities observed in tubular epithelia, the interstitial compartment, and the extracellular matrix of cystic kidneys. In both human and murine PKD, genetic background appears to modulate the renal cystic phenotype. In murine models, these putative modifying effects have been dissected into discrete factors called quantitative trait loci and genetically mapped. Several lines of experimental evidence support the hypothesis that PKD genes and their modifiers may define pathways involved in cystogenesis and PKD progression. Among the various pathway abnormalities described in murine PKD, recent provocative data indicate that structural and/or functional defects in the primary apical cilia of tubular epithelia may play a key role in PKD pathogenesis. This review describes the most widely studied murine models; highlights the data regarding specific gene defects and genetic modifiers; summarizes the data from these models that have advanced our understanding of PKD pathogenesis; and examines the effect of various therapeutic interventions in murine PKD.
Insights
Murine models of polycystic kidney disease (PKD) closely mimic human disease, offering insights into cyst development and potential therapies. Research highlights genetic modifiers and ciliary defects in PKD pathogenesis.
Area of Science:
- Nephrology
- Genetics
- Molecular Biology
Background:
- Polycystic kidney disease (PKD) is a genetic disorder characterized by cyst formation in the kidneys.
- Numerous mouse and rat models (murine models) exist, engineered to study human PKD genes.
- These models exhibit phenotypes similar to human PKD, including tubular, interstitial, and extracellular matrix abnormalities.
Purpose of the Study:
- To review widely studied murine models of PKD.
- To highlight genetic defects and modifiers influencing PKD.
- To examine therapeutic interventions in murine PKD models.
Main Methods:
- Analysis of spontaneous and engineered murine models of PKD.
- Genetic mapping of quantitative trait loci (QTLs) to identify modifiers.
- Review of experimental data on PKD pathogenesis and therapeutic effects.
Main Results:
- Murine PKD models closely recapitulate human disease phenotypes.
- Genetic background significantly modulates renal cystic abnormalities.
- Defects in primary cilia of tubular epithelia are implicated in PKD pathogenesis.
Conclusions:
- Murine models are invaluable for understanding PKD pathogenesis and progression.
- Genetic modifiers and ciliary function are key areas for therapeutic development.
- Therapeutic interventions show promise in preclinical murine studies.
