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Journal of Lipid Research, Vol. 45, 2132-2137, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Hypercholesterolemia in ENU-induced mouse mutants

Manuela Mohr^*, Martina Klempt^*, Birgit Rathkolb^*, Martin Hrabé de Angelis, Eckhard Wolf^* and Bernhard Aigner^1,*

^* Institute of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-University, Munich, Germany
Institute of Experimental Genetics, GSF Research Center for Environment and Health, Neuherberg, Germany

¹ To whom correspondence should be addressed. e-mail: 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 performed on more than 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 C3HeB/FeJ mice we identified more than 100 animals consistently showing hypercholesterolemia. Transmission of the altered phenotype to the subsequent generations led to the production of nine hypercholesterolemic lines. A single line showed further obvious deviations in the analysis of additional clinical chemistry blood parameters.

Thus, the lines produced will contribute to the search for alleles that selectively cause primary hypercholesterolemia.

Abbreviations: C3H, C3HeB/FeJ [inbred mouse strain]; ENU, N-ethyl-N-nitrosourea; Gn, generation number; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol

Supplementary key words cholesterol • ethylnitrosourea • high density lipoproteins • low density lipoproteins • phenotype-driven screen

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