Podocyte proteins in Galloway-Mowat syndrome.

Abstract

Galloway-Mowat syndrome is an autosomal recessive disorder characterized by early onset nephrotic syndrome and central nervous system anomalies. Mutations in podocyte proteins, such as nephrin, alpha-actinin 4, and podocin, are associated with proteinuria and nephrotic syndrome. The genetic defect in Galloway-Mowat syndrome is as yet unknown. We postulated that in Galloway-Mowat syndrome the mutation would be in a protein that is expressed both in podocytes and neurons, such as synaptopodin, GLEPP1, or nephrin. We therefore analyzed kidney tissue from normal children (n=3), children with congenital nephrotic syndrome of the Finnish type (CNF, n=3), minimal change disease (MCD, n=3), focal segmental glomerulosclerosis (FSGS, n=3), and Galloway-Mowat syndrome (n=4) by immunohistochemistry for expression of synaptopodin, GLEPP1, intracellular domain of nephrin (nephrin-I), and extracellular domain of nephrin (nephrin-E). Synaptopodin, GLEPP1, and nephrin were strongly expressed in normal kidney tissue. Nephrin was absent, and synaptopodin and GLEPP1 expression were decreased in CNF. The expression of all three proteins was reduced in MCD and FSGS; the decrease in expression being more marked in FSGS. Synaptopodin, GLEPP1, and nephrin expression was present, although reduced in Galloway-Mowat syndrome. We conclude that the reduced expression of synaptopodin, GLEPP1, and nephrin in Galloway- Mowat syndrome is a secondary phenomenon related to the proteinuria, and hence synaptopodin, GLEPP1, and nephrin are probably not the proteins mutated in Galloway-Mowat syndrome.

• Authors: T Srivastava, J M Whiting, R E Garola, M J Dasouki, V Ruotsalainen, K Tryggvason, R Hamed, U S Alon
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 16 Issue 12 Pg. 1022-9 (Dec 2001) ISSN: 0931-041X [Print] Germany
• PMID: 11793093 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Microfilament Proteins
• Proteins
• SYNPO protein, human
• nephrin
• PTPRO protein, human
• Protein Tyrosine Phosphatases
• Receptor-Like Protein Tyrosine Phosphatases, Class 3

Topics

• Central Nervous System (abnormalities)
• Female
• Humans
• Immunohistochemistry
• Infant
• Infant, Newborn
• Kidney Glomerulus (metabolism, pathology)
• Male
• Membrane Proteins (metabolism)
• Microfilament Proteins (metabolism)
• Nephrotic Syndrome (metabolism)
• Protein Tyrosine Phosphatases (metabolism)
• Proteins (metabolism)
• Receptor-Like Protein Tyrosine Phosphatases, Class 3
• Syndrome