DN
ReninAAV, Unx, db/db model of accelerated diabetic nephropathy
Accelerated type 2 diabetic kidney disease combining hypertension, reduced renal mass and obesity-driven diabetes.
Background and rationale
Combining renin overexpression by AAV, unilateral nephrectomy and the leptin receptor-deficient db/db mouse superimposes hypertension and hyperfiltration on obesity-related type 2 diabetes. The result is an aggressive phenotype with heavy albuminuria, glomerulosclerosis and interstitial fibrosis within a few months, closer to advanced human diabetic kidney disease than db/db alone.
Typical study design
- Sequential ReninAAV delivery and unilateral nephrectomy in db/db mice
- db/+ or vehicle-AAV control arms
- Blood pressure monitoring by CODA tail cuff
- Stratified randomisation on albuminuria before treatment start
Readouts
- Urinary albumin-creatinine ratio and tubular injury markers
- Plasma creatinine, BUN, cystatin C, glucose and HbA1c
- Systolic blood pressure by CODA tail cuff
- PAS and Sirius red histology with AI-assisted glomerulosclerosis and fibrosis scoring
- Multiplex immunofluorescence and RNAscope in situ hybridization
- Single nuclei RNA sequencing and 10x spatial transcriptomics
Interested in this model?
We will walk you through severity levels, group sizes, dosing windows and endpoints, and propose a design matched to your compound.