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Updated: May 29, 2026
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Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
Published on: May 9, 2025
Mouse model of proximal tubule endocytic dysfunction
Kathrin Weyer1, Tina Storm, Jingdong Shan
1Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
Summary
New mouse models with genetic ablation of megalin and cubilin are now available for studying kidney protein reabsorption. These viable mice enable detailed analysis of proximal tubulopathies involving disrupted endocytosis.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- The megalin/cubilin receptor complex is crucial for protein reabsorption in kidney proximal tubules.
- Existing megalin-deficient mouse models have poor viability, limiting research.
Purpose of the Study:
- To generate viable megalin- and/or cubilin-deficient mice using a conditional Cre-loxP system.
- To establish a new animal model for studying kidney proximal tubulopathies.
Main Methods:
- Conditional Cre-loxP system with Wnt4 promoter-driven Cre.
- Analysis of megalin/cubilin expression via qRT-PCR, Western blotting, and immunohistochemistry.
- Assessment of renal albumin uptake and urinary protein excretion.
Main Results:
- Viable, fertile megalin/cubilin double-deficient mice were generated.
- Megalin and/or cubilin expression was reduced by over 89%.
- Mice exhibited increased excretion of megalin/cubilin ligands, including albumin and transferrin.
Conclusions:
- Efficient genetic ablation of megalin, cubilin, or both was achieved.
- The viable double-deficient mice allow for large-scale group analysis.
- These mice are valuable models for proximal tubulopathies with disrupted endocytosis.
