Large-scale albuminuria screen for nephropathy models in chemically induced mouse mutants.
OBJECTIVE
Phenotype-driven screening of a great pool of randomly mutant mice and subsequent selection of animals showing symptoms equivalent to human kidney diseases may result in the generation of novel suitable models for the study of the pathomechanisms and the identification of genes involved in kidney dysfunction.


METHODS
We carried out a large-scale analysis of ethylnitrosourea (ENU)-induced mouse mutants for albuminuria by using qualitative SDS-polyacrylamide gel electrophoresis.


RESULTS
The primary albuminuria screen preceded the comprehensive phenotypic mutation analysis in a part of the mice of the Munich ENU project to avoid loss of mutant animals as a consequence of prolonged suffering from severe nephropathy. The primary screen detected six confirmed phenotypic variants in 2,011 G1 animals screened for dominant mutations and no variant in 48 G3 pedigrees screened for recessive mutations. Further breeding experiments resulted in two lines showing a low phenotypic penetrance of albuminuria. The secondary albuminuria screen was carried out in mutant lines which were established in the Munich ENU project without preceding primary albuminuria analysis. Two lines showing increased plasma urea levels were chosen to clarify if severe kidney lesions are involved in the abnormal phenotype. This analysis revealed severe albuminuria in mice which are affected by a recessive mutation leading to increased plasma urea and cholesterol levels.


CONCLUSIONS
Thus, the phenotypic selection of ENU-induced mutants according to the parameter proteinuria in principle demonstrates the feasibility to identify nephropathy phenotypes in ENU-mutagenized mice.
Rathkolb
Birgit
B
Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich, Germany.
Tran
Tuyen V
TV
Klempt
Martina
M
Hrabé de Angelis
Martin
M
Wanke
Rudiger
R
Wolf
Eckhard
E
Aigner
Bernhard
B
D000419:Albuminuria / Q000235:genetics / Q000503:physiopathology* / Q000662:veterinary*; D000477:Alkylating Agents / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000008:administration & dosage; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016296:Mutagenesis; D010375:Pedigree; D010641:Phenotype; D011507:Proteinuria
D000477:Alkylating Agents; D005038:Ethylnitrosourea