Drug Testing in Rodent PKD Models

Overview

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.

Available models

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 (Pkhd1^del2/del2 and Pkhd1^lsl/lsl mice)
• Murine model of ADPKD type 1 (Pkd1^f/f:ERCre)
• Murine model of ADPKD type 2 (Pkd2^-/WS25 mice)

Outcome measures

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