Abstract: SA-PO223

Novel Genetic Modeling of Podocyte Diseases and Early Mesodermal Development

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology

Authors

  • Drummond, Bridgette, University of Notre Dame, Notre Dame, Indiana, United States
  • Wingert, Rebecca A., University of Notre Dame, Notre Dame, Indiana, United States
Background

Specialized renal epithelial cells known as podocytes create an essential filter that when comprimised is causitive of numerous kidney diseases. Podocyte morphology and genetic regulatory systems are conserved in zebrafish, making them a simplified and accessible model to study podocyte development and disease states.

Methods

To systematically elucidate the network of podocyte development genes, we have developed a haploid ethylnitrosurea (ENU) screen to identify novel podocyte regulators.

Results

In the emerging panel of these new congenital models of podocyte genesis, we have isolated classes of defects including podocyte abrogation, reduction of podocyte number suggesting alterations in proliferation or survival of the lineage, and delayed differentiation. Of these, one mutant that has been identified has a complete loss or significant reduction of several established podocyte markers. In conjunction with this, the pronephros is proximally abrogated and has a dramatic decrease in several solute-transporter cells that distinguish both proximal and distal tubule segments. Interestingly, several known renal progenitors that demarcate the intermediate mesoderm also reduced in these mutants.

Conclusion

Elucidation of the genetic lesions in these mutants will provide valuable insights into the molecular components that are involved in podocyte development, and possibly provide models for congenital defects and other kidney diseases.

Funding

  • NIDDK Support