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Am J Physiol Renal Physiol (January 30, 2007). doi:10.1152/ajprenal.00213.2006
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Submitted on June 13, 2006
Accepted on January 18, 2007

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

Bernhard Aigner1*, Birgit Rathkolb1, Nadja Herbach2, Elisabeth Kemter2, Christina Schessl1, Matthias Klaften3, Martina Klempt4, Martin Hrabe de Angelis5, Rüdiger Wanke2, and Eckhard Wolf4

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

* To whom correspondence should be addressed. E-mail: b.aigner{at}gen.vetmed.uni-muenchen.de.

Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ENU mouse mutagenesis project, which is done on 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-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.




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