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Kidney Week

Abstract: FR-PO1029

Loss of Function of EMP2 Does Not Cause Glomerular Disease in Mice

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Donnan, Michael D., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Scott, Rizaldy P., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Onay, Tuncer, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Onay, Ummiye venus, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Tarjus, Antoine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
  • Quaggin, Susan E., Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States
Background

Mutations in the human gene Epithelial Membrane Protein 2 (EMP2) have been linked to childhood-onset nephrotic syndrome (OMIM#615861) with expression reported within podocytes. In mice, the Emp2 gene is necessary for embryo implantation and placental angiogenesis. Its gene product, a tetraspan integral membrane protein, affects various cell behaviors including cell adhesion and migration. To further understand its role in glomerular disease, we studied Emp2 expression and generated cell-specific Emp2 knockout (KO) mice.

Methods

Emp2 mRNA was profiled in various tissues using qRT-PCR analysis. We created a conditional floxed Emp2 allele carrying a lacZ cassette that allows whole-mount β-galactosidase (β-gal) histochemical analysis of Emp2 expression. We created podocyte-specific knockout and null Emp2 mutant mice by breeding floxed Emp2 animals with Nphs1-Cre and EIIa-Cre driver strains, respectively. Emp2 mutant mice were assessed for proteinuria and renal histology.

Results

Based on qRT-PCR analysis, Emp2 expression was highest in lungs, but is expressed in multiple other organs including the kidney. β-gal staining reveals that Emp2 is present in the vasculature. In the kidney, β-gal staining is found in large caliber vessels but is surprisingly absent in glomeruli. By 3 months of age, mice lacking Emp2 within podocytes or globally do not exhibit proteinuria or renal abnormalities.

Conclusion

In contrast to previous reports, we did not observe significant Emp2 expression in podocytes or within the glomerulus. Emp2 deficiency in mice did not cause overt kidney disease. Our data demonstrate a vascular pattern of expression throughout multiple tissues. These findings suggest that Emp2 may have a key endothelial function, which would explain reports implicating Emp2 in placental vascular development and tumor angiogenesis. Our findings do not support a causative role for EMP2 mutations in patients with childhood-onset nephrotic syndrome.