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Abstract: TH-PO777

Characterizing Renal Involvement in Hermansky-Pudlak Syndrome in a Zebrafish Model

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Müller-Deile, Janina, MHH, Hanover, Germany
  • Schenk, Heiko Joachim, MHH, Hanover, Germany
  • Schroder, Patricia Ann, Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, United States
  • Schiffer, Mario, Hannover Medical School, Hannover, Germany
Background


Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive genetic disorder, which is characterized by oculo-cutaneous albinism, a platelet storage pool deficiency as well as a lysosomal accumulation of ceroid lipofuscin. Impaired renal function and proteinuric kidney disease has been reported in some studies but we hypothesize that renal involvement in HPS is underestimated.

Methods

To evaluate proteinuric kidney disease in HPS we used the transgenic zebrafish line Tg(l-fabp:eGFP-DBP). These zebrafish express a fabp-promoter regulated enhanced GFP-labeled vitamin-D-binding-protein that resembles the size of human albumin. The loss of eGFP-DBP from the circulation indicates a dysfunction of the glomerular filtration barrier and can easily be assessed in the eye of the fish. We performed morpholino injection of different HPS isoforms at one to four cell stage of the zebrafish.

Results

Pericardial effusion and yolk sac edema were seen after knockdown of HPS-1, -4 and -5. Knockdown HPS-1 and -5 induced significant of proteinuria at 96 hour post fertilization. To determine whether edema and proteinuria resulted from glomerular defects, we used transmission electron microscopy of the zebrafish pronephros. Intracellular inclusion bodies were mainly seen in podocytes indicating that podocytes are the dominant glomerular cell type effected in HPS. Moreover, podocyte effacement could be detected after knockdown of different HPS isoforms (figure 1).

Conclusion

We established the first animal model to investigate glomerular damage in HPS. Understanding the renal involvement in HPS may allow the use of already existing therapeutic options and could prolong the life expectancy of affected patients.

(figure 1)