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Updated: Jun 22, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes
Sarah E Elzinga1, Stephanie A Eid1, Brett A McGregor2
1Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract:
Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are common complications of type 1 (T1D) and type 2 (T2D) diabetes. However, the mechanisms underlying pathogenesis of these complications are unclear. In this study, we optimized a streptozotocin-induced db/+ murine model of T1D and compared it to our established db/db T2D mouse model of the same C57BLKS/J background. Glomeruli and sciatic nerve transcriptomic data from T1D and T2D mice were analyzed by self-organizing map and differential gene expression analysis. Consistent with prior literature, pathways related to immune function and inflammation were dysregulated in both complications in T1D and T2D mice. Gene-level analysis identified a high degree of concordance in shared differentially expressed genes (DEGs) in both complications and across diabetes type when using mice from the same cohort and genetic background. As we have previously shown a low concordance of shared DEGs in DPN when using mice from different cohorts and genetic backgrounds, this suggests that genetic background may influence diabetic complications. Collectively, these findings support the role of inflammation and indicate that genetic background is important in complications of both T1D and T2D.
Insights
Diabetic kidney disease and neuropathy share inflammatory pathways. Genetic background significantly influences these diabetes complications, impacting gene expression in affected tissues.
Area of Science:
- Endocrinology and Metabolism
- Genetics and Genomics
- Nephrology and Urology
Background:
- Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are prevalent, yet poorly understood, complications of type 1 diabetes (T1D) and type 2 diabetes (T2D).
- Understanding the molecular mechanisms driving these diabetes complications is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the shared and distinct molecular pathways in DKD and DPN across T1D and T2D models.
- To evaluate the influence of genetic background on the pathogenesis of diabetic complications.
Main Methods:
- Utilized streptozotocin-induced T1D (db/+) and established T2D (db/db) mouse models on a C57BLKS/J background.
- Performed transcriptomic analysis on glomeruli and sciatic nerves.
- Employed self-organizing map and differential gene expression analysis to identify key molecular changes.
Main Results:
- Identified dysregulated immune function and inflammation pathways common to both DKD and DPN in T1D and T2D models.
- Observed a high concordance of shared differentially expressed genes (DEGs) within the same genetic background, across complications and diabetes types.
- Highlighted the significant impact of genetic background on DEG patterns, contrasting with previous findings using different mouse cohorts.
Conclusions:
- Inflammation plays a central role in the pathogenesis of DKD and DPN.
- Genetic background is a critical determinant of diabetic complication development and molecular signatures.
- Findings underscore the importance of considering genetic factors in studying and treating diabetes complications.
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