Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models

Bernhard Aigner, Birgit Rathkolb, Nadja Herbach, Elisabeth Kemter, Christina Schessl, Matthias Klaften, Martina Klempt, Martin Hrabé De Angelis, Rüdiger Wanke, Eckhard Wolf

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ethylnitrosourea (ENU) mouse mutagenesis project, which is done on a C3H inbred genetic background, blood samples of more than 15,000 G1 offspring and 500 G3 pedigrees were screened for alterations in clinical-chemical parameters. We identified 44 animals consistently exhibiting increased plasma urea concentrations. Transmission analysis of the altered phenotype of 23 mice to subsequent generations led to the establishment of five mutant lines. Both sexes were affected in these lines. Urinary urea levels were decreased in the mutants. In addition, most mutants showed increased plasma and decreased urinary creatinine levels. Pathological investigation of kidneys from the five mutant lines revealed a broad spectrum of alterations, ranging from no macroscopic and light microscopic kidney alterations to decreased kidney weight-to-body weight ratio, dilation of the renal pelvis, and severe glomerular lesions. Thus screening for elevated plasma urea levels in a large-scale ENU mouse mutagenesis project resulted in the successful establishment of mouse strains which are valuable tools for molecular studies of mechanisms involved in urea excretion or which represent interesting models for kidney diseases.

Original languageEnglish
Pages (from-to)F1560-F1567
JournalAmerican Journal of Physiology - Renal Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • Ethylnitrosourea
  • Nephropathy
  • Renal failure

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