Hypercholesterolemia in ENU-induced mouse mutants

Manuela Mohr, Martina Klempt, Birgit Rathkolb, Martin Hrabé de Angelis, Eckhard Wolf, and Bernhard Aigner

Institute of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-University, Oberschleibheim, Oberschleibheim D-85764

Corresponding Author: b.aigner{at}gen.vetmed.uni-muenchen.de

Hypercholesterolemia is caused by multiple environmental factors and genetic predispositions, and plays an important role in the development and pathogenesis of various human diseases. In this study, we aimed to establish randomly mutant mouse lines showing hypercholesterolemia for their further use in the detection of novel causative alleles. In the Munich ENU mouse mutagenesis project, clinical chemistry blood analysis was carried out on over 15,000 G1 mice and 230 G3 pedigrees of chemically mutagenized mice to detect dominant and recessive mutations leading to an increased plasma total cholesterol level. Using inbred C3H mice, we identified more than 100 animals consistently showing hypercholesterolemia. Transmission of the altered phenotype to the subsequent generations led to the generation of nine hypercholesterolemic lines. A single line showed further obvious deviations in the analysis of additional clinical chemistry blood parameters. Thus, the produced lines will contribute to the search for alleles which selectively cause primary hypercholesterolemia.

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