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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1560    most recent 00213.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Aigner, B. Articles by Wolf, E. Search for Related Content PubMed PubMed Citation Articles by Aigner, B. Articles by Wolf, E.

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

¹Institute of Molecular Animal Breeding and Biotechnology and ²Institute of Veterinary Pathology, Ludwig Maximilians University, Munich; and ³Institute of Experimental Genetics, GSF Research Center for Environment and Health, Neuherberg, Germany

Submitted 13 June 2006 ; accepted in final form 18 January 2007

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.

ethylnitrosourea; nephropathy; renal failure

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				B. Aigner, B. Rathkolb, N. Herbach, M. H. de Angelis, R. Wanke, and E. Wolf Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E232 - E240. [Abstract] [Full Text] [PDF]