PuSH - Publication Server of Helmholtz Zentrum München

Kemter, E.* ; Rathkolb, B.* ; Rozman, J.* ; Hans, W. ; Schrewe, A.* ; Landbrecht, C.* ; Klaften, M.* ; Ivandic, B.* ; Fuchs, H. ; Gailus-Durner, V. ; Klingenspor, M.* ; Hrabě de Angelis, M. ; Wolf, E.* ; Wanke, R.* ; Aigner, B.*

Novel missense mutation of uromodulin in mice causes renal dysfunction with alterations in urea handling, energy, and bone metabolism.

Am. J. Physiol.-Renal Physiol. 297, F1391-F1398 (2009)
Publ. Version/Full Text DOI PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
Uromodulin-associated kidney disease is a heritable renal disease in humans caused by mutations in the uromodulin (UMOD) gene. The pathogenesis of the disease is mostly unknown. In this study, we describe a novel chemically induced mutant mouse line termed Umod(A227T) exhibiting impaired renal function. The A227T amino acid exchange may impair uromodulin trafficking, leading to dysfunction of thick ascending limb cells of Henle's loop of the kidney. As a consequence, homozygous mutant mice display azotemia, impaired urine concentration ability, reduced fractional excretion of uric acid, and a selective defect in concentrating urea. Osteopenia in mutant mice is presumably a result of chronic hypercalciuria. In addition, body composition, lipid, and energy metabolism are indirectly affected in heterozygous and homozygous mutant Umod(A227T) mice, manifesting in reduced body weight, fat mass, and metabolic rate as well as reduced blood cholesterol, triglycerides, and nonesterified fatty acids. In conclusion, Umod(A227T) might act as a gain-of-toxic-function mutation. Therefore, the Umod(A227T) mouse line provides novel insights into consequences of disturbed uromodulin excretion regarding renal dysfunction as well as bone, energy, and lipid metabolism.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Kidney ; N-ethyl-n-nitrosourea ; Renal Disease ; Umod
ISSN (print) / ISBN 0002-9513
e-ISSN 1522-1466
Journal American Journal of Physiology - Renal Physiology
Quellenangaben Volume: 297, Issue: 5, Pages: F1391-F1398 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place Bethesda
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)