Abstract: TH-PO594

A Mouse Model of Tsc Renal Cystic Disease

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Bissler, John J., University of Tennessee, Le Bonheur Children's Hospital and St. Jude Children's Research Hospital, Memphis, Tennessee, United States
  • Zahedi, Kamyar A., University of Cincinnati, Cincinnati, Ohio, United States
  • Barone, Sharon L., University of Cincinnati, Cincinnati, Ohio, United States
  • Soleimani, Manoocher, University of Cincinnati, Cincinnati, Ohio, United States
Background

Tuberous sclerosis complex (TSC) renal cystic disease affects over 500,000 patients world-wide. There are five patterns of TSC-associated renal cystic disease, and they are the macrocystic diseases including polycystic, cortical cystic, multicystic, focal cystic diseases, and microcystic disease. The cysts can have a simple single cellular layer, have a multiply layer or even papillary histology. Although the basic histology has been described, the cystogenic mechanism in TSC is poorly understood.

Methods

To begin to better understand this cystic disease process, we created a mouse model of TSC renal cystic disease by targeting principle cells by using aquaporin 2-driven Cre recombinase expression to delete the floxed Tsc2 gene. Double immunofluorescence labeling was performed to determine the identity of cyst epithelium.

Results

In this cell specific model, we identify the similar histological characteristics of the renal cystic epithelium as occurs in the human. Interestingly, the cyst epithelium was predominantly comprised of intercalated cells as determined by intense and uniform apical expression of H+-ATPase in both mouse and human. There was no expression of AQP-2, NHE-3, NBC-e1, NCC or Na-K-ATPase, indicating the absence of principal, proximal tubule, distal convoluted and thick ascending limb epithelial cells in the cyst wall. The cysts in human and mouse also exhibited a significant decrease in cilia expression.

Conclusion

We have developed a mouse model that resembles human TSC-associated renal cystic disease. This TSC renal cystic disease in both the mouse model and human exhibits significant histolopathological differences compared to other renal cystic diseases. These differences raise the possibility that therapies like V2 receptor antagonism may not have similar efficacy.

Funding

  • Other U.S. Government Support