Rodent PKD-Targeted Services

The Model Systems Core offers rodent PKD-targeted services to PKD researchers both at Mayo Clinic and at other institutions.

While C. elegans and zebrafish models are convenient for rapid drug screening, testing of promising therapies in well-characterized, orthologous rodent models of polycystic kidney disease is necessary to establish the basis for clinical trials.

In addition, rodent models anatomically and physiologically mimic humans more closely than do C. elegans and zebrafish models, providing a platform to study PKD-related renal and extrarenal pathomechanisms at the organ level.

Services

The Model Systems Core offers several fee-based rodent PKD-targeted services:

  • Chemical and natural compound testing in rodent models of PKD. Depending on the mechanism of action or the intended effect of a certain drug, various rodent models and drug doses can be used to evaluate PKD-related treatment outcomes. The Model System Core offers expert advice about the best-suited model and appropriate dose regimens.
  • Evaluation of modifier gene effects. Studies have shown that mutations in genes associated with PKD pathways can either alleviate or worsen PKD progression. Crossing murine models of the gene of interest with well-established PKD models and evaluating PKD-related phenotypes can decipher the significance of such modifier genes. [1, 2]
  • Training on rodent-related technologies.
  • Imaging-based, histological and physiological characterization of PKD-related phenotypes. This service is utilized as part of the compound testing and modifier evaluation service. However, it can be requested to characterize any novel model or other PKD-related rodent models. Services include:
    • Imaging-based characterization, including renal and extrarenal gross organ structure analysis, total kidney and liver volume calculations, and renal microvasculature and biliary tree analysis. Techniques include ultrasound, micro-CT, MRI and data analysis.
    • Histological characterization, including morphometric analysis of cystic and fibrotic volume and analysis of tubular cyst origin. Techniques include H&E, Masson trichrome, Picro Sirius Red, immunofluorescence staining and data analysis.
    • Physiological characterization, including renal concentrating capacity, blood pressure, and renal and liver function. Techniques include metabolic cages, tail-cuff analysis, blood chemistry, electrolytes, immunoassay and gas analysis.

The Model Systems Core offers training on any of the techniques used and general rodent-related training, such as line maintenance, line crosses and genotyping.

Related publications

  1. Olson RJ, Hopp K, Wells H, Smith JM, Furtado J, Constans MM, Escobar DL, Geurts AM, Torres VE, Harris PC. Synergistic genetic interactions between Pkhd1 and Pkd1 result in an ARPKD-like phenotype in murine models. Journal of the American Society of Nephrology. 2019; doi:10.1681/ASN.2019020150.
  2. Gainullin VG, Hopp K, Ward CJ, Hommerding CJ, Harris PC. Polycystin-1 maturation requires polycystin-2 in a dose-dependent manner. The Journal of Clinical Investigation. 2015; doi:10.1172/JCI76972.

Contact

Email us for more information about rodent PKD-targeted services.