Within the kidney, thousands of structures known as glomeruli filter harmful or unnecessary substances out of blood and into the urine. During the condition known as focal segmental glomerulosclerosis (FSGS), scar tissue forms in segments of some of the glomeruli. This results in the persistent release of protein from the urine and progression to renal failure. Despite a growing understanding of the genes involved in FSGS, a clear genetic diagnosis cannot be made in the vast majority of patients. In a study appearing online in April, in advance of print publication in the May issue of the Journal of Clinical Investigation, Andrey Shaw and colleagues from Washington University, St. Louis, Missouri tested whether combinations of genetic heterozygosity of genes that alone do not result in clinical kidney disease could function together to cause FSGS.

The authors crossed mice heterozygous for the gene Cd2ap with mice heterozygous for the kidney-relevant genes Fyn, Synpo or Neph1. They found that animals with bigenic heterozygosity for Cd2ap with Fyn or Synpo, but not Neph 1, had increased protein release in their urine and clinical changes within their kidney consistent with FSGS. This suggests that combined mutations of genes that encode the proteins Cd2ap, Fyn or Synpo may account for disease in some patients with FSGS.

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TITLE: A bigenic mouse model of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin

AUTHOR CONTACT:
Andrey S. Shaw
Washington University School of Medicine, St. Louis, Missouri, USA

View the PDF of this article at: https://www.the-jci/article.php?id=27400

Contact: Brooke Grindlinger
Journal of Clinical Investigation