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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Med. | doi: 10.3389/fmed.2019.00189

Genetic deletion of Emp2 does not cause proteinuric kidney disease in mice

  • 1Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, United States
  • 2Division of Nephrology & Hypertension, Feinberg School of Medicine, Northwestern University, United States

Nephrotic syndrome is one of the most common glomerular diseases in children and can be classified on the basis of steroid responsiveness. While multiple genetic causes have been discovered for steroid resistant nephrotic syndrome, the genetics of steroid sensitive nephrotic syndrome remains elusive. Mutations in Epithelial Membrane Protein 2 (EMP2), a member of the GAS3/PMP22 tetraspan family of proteins, were recently implicated as putative monogenic cause of steroid sensitive nephrotic syndrome. We investigated this hypothesis by developing Emp2 reporter and knockout mouse models. In lacZ reporter mice (engineered to drive expression of the enzyme -galactosidase under the control of the endogenous murine Emp2 promoter), Emp2 promoter activity was not observed in podocytes but was particularly prominent in medium- and large-caliber arterial vessels in the kidney and other tissues where it localizes specifically in vascular smooth muscle cells but not in the endothelium. Strong Emp2 expression was also found in non-vascular smooth muscle cells found in other organs like the stomach, bladder, and uterus. Global and podocyte-specific Emp2 knockout mice were viable and did not develop nephrotic syndrome showing no evidence of abnormal glomerular histology or ultrastructure. Altogether, our results do not support that loss of function of EMP2 represent a monogenic cause of proteinuric kidney disease. However, the expression pattern of Emp2 indicates that it may be relevant in smooth muscle function in various organs and tissues including the vasculature.

Keywords: EMP2, Nephrotic syndrome (NS), Proteinuria, Smooth muscle, vascular

Received: 24 May 2019; Accepted: 09 Aug 2019.

Copyright: © 2019 Donnan, Scott, Onay, Tarjus, Onay and Quaggin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Susan E. Quaggin, Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, 60611, Illinois, United States,