Large-scale albuminuria screen for nephropathy models in chemically induced mouse mutants

Background/Aim: 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. Conclusion: 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. Copyright (C) 2005 S. Karger
AG, Basel.