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A Simplified Model of Adenine-Induced Chronic Kidney Disease Using SKH1 Mice
Benjamin W French1, Joshua D Breidenbach1,2, Shereen G Yassine1,3
1Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA.
Abstract:
Commonly used adenine-induced chronic kidney disease (CKD) murine models often employ C57BL/6 mice; however, this strain has inherent limitations due to its natural resistance to developing key pathological features of CKD, such as tubulointerstitial fibrosis and inflammation. There have been attempts to overcome these barriers by using multiple concentrations of adenine-supplemented diets or by performing prolonged experiments up to 20 weeks. Here, we demonstrate that SKH1 Elite mice develop clinically relevant CKD phenotypes (e.g., polyuria, proteinuria, inflammation, and renal fibrosis) over the course of only 6 weeks of low-dose (0.15%) adenine supplementation. As a docile, immunocompetent, and hairless strain, SKH1 Elite mice offer several logistical advantages over C57BL/6 mice, including ease of handling and the ability to study dermal conditions, which are often secondary to CKD.
Insights
SKH1 Elite mice offer a superior model for studying chronic kidney disease (CKD). This strain develops key CKD pathologies like renal fibrosis and inflammation within six weeks using low-dose adenine, overcoming limitations of C57BL/6 mice.
Area of Science:
- Nephrology
- Animal Models
- Toxicology
Background:
- Chronic kidney disease (CKD) murine models are crucial for research.
- C57BL/6 mice, commonly used, exhibit resistance to key CKD pathologies like tubulointerstitial fibrosis and inflammation.
- Existing methods to induce CKD in mice involve high adenine concentrations or prolonged study durations (up to 20 weeks).
Purpose of the Study:
- To establish a more effective and efficient murine model for studying chronic kidney disease (CKD).
- To evaluate the utility of SKH1 Elite mice in developing clinically relevant CKD phenotypes.
- To highlight the advantages of SKH1 Elite mice over C57BL/6 mice for CKD research.
Main Methods:
- Utilized SKH1 Elite mice for adenine-induced chronic kidney disease (CKD) modeling.
- Administered a low-dose (0.15%) adenine-supplemented diet.
- Conducted experiments over a 6-week period.
Main Results:
- SKH1 Elite mice developed significant CKD phenotypes, including polyuria, proteinuria, inflammation, and renal fibrosis.
- These clinically relevant pathologies were observed within a 6-week timeframe.
- Low-dose adenine supplementation proved effective in inducing CKD in this strain.
Conclusions:
- SKH1 Elite mice provide a robust and time-efficient model for studying chronic kidney disease (CKD).
- This strain overcomes the limitations of C57BL/6 mice in developing key CKD features.
- The hairless, immunocompetent nature of SKH1 Elite mice offers logistical benefits and potential for studying co-occurring dermal conditions in CKD.
