Hypercholesterolemia in ENU-induced mouse mutants

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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2132-2137
Number of pages6
JournalJournal of Lipid Research
Volume45
Issue number11
DOIs
StatePublished - Nov 2004
Externally publishedYes

Keywords

  • Cholesterol
  • Ethylnitrosourea
  • High density lipoproteins
  • Low density lipoproteins
  • Phenotype-driven screen

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