title: Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models.
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.
authors.affiliation: Institute of Molecular Animal Breeding and BiotechnologyInstitute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich, Germany. b.aigner@gen.vetmed.uni-muenchen.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Aigner
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Nadja
authors.initials: N
authors.lastname: Herbach
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kemter
authors.forename: Christina
authors.initials: C
authors.lastname: Schessl
authors.forename: Matthias
authors.initials: M
authors.lastname: Klaften
authors.forename: Martina
authors.initials: M
authors.lastname: Klempt
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Wanke
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
mesh_terms: D000818:Animals; D001835:Body Weight; D002874:Chromosome Mapping; D003404:Creatinine / Q000097:blood / Q000652:urine; D005038:Ethylnitrosourea; D005260:Female; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D007682:Kidney Pelvis / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009929:Organ Size; D010641:Phenotype; D014508:Urea / Q000097:blood*
chemical_list: D014508:Urea; D003404:Creatinine; D005038:Ethylnitrosourea