title: Hypercholesterolemia in ENU-induced mouse mutants.
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.
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mohr
authors.forename: Martina
authors.initials: M
authors.lastname: Klempt
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Bernhard
authors.initials: B
authors.lastname: Aigner
mesh_terms: D000483:Alleles; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D005038:Ethylnitrosourea; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006937:Hypercholesterolemia / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D016296:Mutagenesis; D009153:Mutagens; D009154:Mutation; D010641:Phenotype
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D009153:Mutagens; D002784:Cholesterol; D005038:Ethylnitrosourea