Drug Testing in Rodent PKD Models
While C. elegans and zebrafish models are very convenient for rapid drug screening, testing of promising therapies in well-characterized, orthologous rodent models of autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD) is necessary to establish the basis for clinical trials.
To accurately evaluate a potential therapy, the chosen model must demonstrate a consistent disease course (i.e., moderately progressive time course — not too fast, not too slow) that is appropriate for testing an intervention.
Four models exhibit the above characteristics and are used by the core for drug testing:
- Rat model of ARPKD (PCK rat)
- Murine models of ARPKD (Pkhd1del2/del2 and Pkhd1lsl/lsl mice)
- Murine model of ADPKD type 1 (Pkd1f/f:ERCre)
- Murine model of ADPKD type 2 (Pkd2-/WS25 mice)
Depending on the mechanism of action or the intended effect of a particular drug, a number of technologies may be used to measure or determine the outcome of an intervention. The core has available the following methods for evaluating results in rodent models:
- Dosing regimens
- Renal function
- Renal concentrating capacity
- Analysis of liver function
- Continuous monitoring of blood pressure
- Histomorphometric analysis
- Bioluminescence imaging
- Ultrasonography of kidney and liver
- Magnetic resonance (MR) imaging of kidney and liver
- Micro-CT for three-dimensional analysis of renal microvasculature and the biliary tree
- Microdissection of cysts, tubules and bile duct units
Of these methods, histomorphometric analysis and renal function are the most commonly used ways to determine the efficacy of a particular treatment.
Submit an email inquiry to the core about rodent services