PUBLICATION
Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria
- Authors
- Korstanje, R., Deutsch, K., Bolanos-Palmieri, P., Hanke, N., Schroder, P., Staggs, L., Bräsen, J.H., Roberts, I.S., Sheehan, S., Savage, H., Haller, H., Schiffer, M.
- ID
- ZDB-PUB-160330-9
- Date
- 2016
- Source
- Journal of the American Society of Nephrology : JASN 27(11): 3271-3277 (Journal)
- Registered Authors
- Keywords
- genetic renal disease, podocyte, proteinuria
- MeSH Terms
-
- Animals
- Female
- Gene Deletion*
- Humans
- Kynurenine 3-Monooxygenase/genetics*
- Kynurenine 3-Monooxygenase/physiology
- Male
- Mice
- Mice, Inbred C57BL
- Proteinuria/enzymology*
- Proteinuria/genetics*
- Zebrafish
- PubMed
- 27020856 Full text @ J. Am. Soc. Nephrol.
Citation
Korstanje, R., Deutsch, K., Bolanos-Palmieri, P., Hanke, N., Schroder, P., Staggs, L., Bräsen, J.H., Roberts, I.S., Sheehan, S., Savage, H., Haller, H., Schiffer, M. (2016) Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria. Journal of the American Society of Nephrology : JASN. 27(11):3271-3277.
Abstract
Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown ofkmoexpression in zebrafish and genetic deletion ofKmoin mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping