CKD
Col4a3 knockout model of Alport syndrome
Genetic model of hereditary glomerular basement membrane disease with progressive kidney failure.
Background and rationale
Loss of the alpha-3 chain of type IV collagen destabilises the glomerular basement membrane, producing the lamellated basement membrane, progressive proteinuria and glomerulosclerosis characteristic of Alport syndrome. Disease onset and progression are predictable, making the model well suited to gene therapy, RNA therapeutics and antifibrotic programmes.
Typical study design
- Genotype-confirmed knockout and littermate wild-type controls
- Treatment start before or after onset of albuminuria
- Longitudinal albuminuria and GFR follow-up
- Survival or fixed-timepoint endpoints
Readouts
- Urinary albumin-creatinine ratio; plasma creatinine, BUN and cystatin C
- Transdermal GFR measurement
- PAS and Sirius red histology with AI-assisted scoring
- Electron microscopy and Magnephy super-resolved 3D imaging of the basement membrane
- Collagen IV chain immunofluorescence and RNAscope in situ hybridization
- Single nuclei RNA sequencing and 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.