Related Experiment Video
Updated: Jan 4, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Sex differences in progression of diabetic nephropathy in OVE26 type 1 diabetic mice
Wanning Wang1, Saizhi Jiang2, Xiaoqiang Tang3
1Department of Nephrology, the First Hospital of Jilin University, Changchun 130021, China; Pediatric Research Institute, Department of Pediatrics, the University of Louisville School of Medicine, Louisville, KY 40292, USA.
Aims:
OVE26 mice (FVB background), genetically overexpressing calmodulin in pancreatic beta cells, develop early onset type 1 diabetes, leading to progressive diabetic nephropathy (DN), with features of established human DN. The role of gender in characteristics of renal lesions has remained unexplored.
Methods:
Male and female OVE26 mice were compared to age and sex matched wild-type, nondiabetic FVB mice at ages of 4, 12, 24 and 36 weeks. Nephropathy was examined by measuring urine albumin-to-creatinine ratio, histopathology, expression of pathological markers and immunochemistry in the same cohort of mice.
Results:
Progression of diabetic kidney disease was evident first in the OVE26 glomerulus, initially as mesangial matrix expansion at 4 weeks followed by loss of podocytes, glomerular volume expansion and severe albuminuria at 12 weeks. Tubule dilation and initiation of interstitial fibrosis did not become significant until 24 weeks. T-lymphocyte infiltration into the renal parenchyma appeared at 36 weeks. OVE26 female mice developed more advanced DN than male OVE26 mice, such as more severe albuminuria, greater podocyte loss, additional fibrosis and significantly more inflammatory cell infiltration. The female OVE26 mice had lowest level of plasma estradiol in all 36 weeks old mice, as well as renal estrogen receptors.
Conclusions:
This demonstration of the role of gender, combined with the detailed characterization of DN progression illustrates the value of OVE26 mice for understanding gender effects on DN and provides the basis for researchers to better select the age and sex of OVE26 mice in future studies of type 1 DN.
Research In Context:
What is already known about this subject? What is the key question? What are the new findings? How might this impact on clinical practice in the foreseeable future?
Insights
Female OVE26 mice show more severe diabetic nephropathy (DN) progression than males, with greater albuminuria and inflammation. This highlights gender differences in DN and informs future research using OVE26 mouse models.
Area of Science:
- Nephrology
- Endocrinology
- Immunology
Background:
- OVE26 mice overexpress calmodulin, developing type 1 diabetes and diabetic nephropathy (DN) similar to human conditions.
- The influence of gender on renal lesion characteristics in OVE26 mice has not been previously investigated.
Purpose of the Study:
- To investigate the role of gender in the progression of diabetic nephropathy in OVE26 mice.
- To characterize the temporal development of renal lesions in male and female OVE26 mice.
Main Methods:
- Comparison of male and female OVE26 mice with wild-type FVB mice at 4, 12, 24, and 36 weeks.
- Assessment of nephropathy through urine albumin-to-creatinine ratio, histopathology, and marker expression.
Main Results:
- Diabetic kidney disease (DKD) progression included mesangial expansion, podocyte loss, and albuminuria by 12 weeks in OVE26 mice.
- Female OVE26 mice exhibited more severe DN, including greater albuminuria, podocyte loss, fibrosis, and inflammation.
- Lower estradiol levels and renal estrogen receptors were observed in female OVE26 mice.
Conclusions:
- Gender significantly influences diabetic nephropathy progression in OVE26 mice, with females experiencing more severe disease.
- OVE26 mice are a valuable model for studying gender-specific effects in type 1 DN.
- Findings provide a basis for selecting age and sex in future OVE26 mouse studies.
