Shared and Distinct Renal Transcriptome Signatures in 3 Standard Mouse Models of Chronic Kidney Disease
Adam B Marstrand-Jørgensen1, Frederikke Emilie Sembach2, Stine Thorhauge Bak2
1Gubra A/S, Hørsholm, Denmark, amj@gubra.dk.
Nephron
|February 14, 2024
Summary
Three common chronic kidney disease (CKD) mouse models share molecular changes but also have unique transcriptional signatures. Understanding these differences is crucial for preclinical CKD research and drug discovery.
Area of Science:
- Nephrology
- Translational Medicine
- Genomics
Background:
- Chronic kidney disease (CKD) research relies on various mouse models.
- Head-to-head comparisons are needed to understand model-specific molecular changes.
Purpose of the Study:
- To compare renal transcriptome signatures across three standard preclinical CKD mouse models.
- To identify shared and distinct molecular alterations in CKD models.
Main Methods:
- Utilized unilateral ureter obstruction (UUO), unilateral ischemic-reperfusion injury (uIRI), and adenine-diet induced (ADI) mouse models.
- Collected plasma biochemistry, kidney histology, and RNA sequencing data at multiple time points.
- Analyzed macrophage infiltration and fibrosis markers.
Main Results:
- All models showed increased macrophage infiltration and fibrosis.
- Extensive renal differentially expressed genes (≥11,000) were observed in all models.
- Significant overlap in transcriptomic signatures was found, alongside model-specific gene expression profiles.
Conclusions:
- The UUO, uIRI, and ADI models exhibit substantial commonalities in renal transcriptome profiles.
- Model-specific transcriptional signatures are important considerations for preclinical CKD research and drug discovery.
- Choosing the appropriate model is critical for successful target identification and therapeutic development.
