A new mouse mutant for the LDL receptor identified using ENU mutagenesis.
Document Type
Article
Publication Date
2008
Keywords
Animals, Base-Sequence, Disease-Models-Animal, Ethylnitrosourea, Hyperlipoproteinemia-Type-II, Mice-Inbred-C57BL, Mice-Inbred-DBA, Mice-Knockout, Molecular-Sequence-Data, Mutagenesis, Mutagens, Mutation-Missense, Receptors-LDL
First Page
2452
Last Page
2462
JAX Source
J Lipid Res 2008 Nov; 49(11):2452-62.
Abstract
In an effort to discover new mouse models of cardiovascular disease using N-ethyl-N-nitrosourea (ENU) mutagenesis followed by high-throughput phenotyping, we have identified a new mouse mutation, C699Y, in the LDL receptor (Ldlr), named wicked high cholesterol (WHC). When WHC was compared with the widely used Ldlr knockout (KO) mouse, notable phenotypic differences between strains were observed, such as accelerated atherosclerotic lesion formation and reduced hepatosteatosis in the ENU mutant after a short exposure to an atherogenic diet. This loss-of-function mouse model carries a single base mutation in the Ldlr gene on an otherwise pure C57BL/6J (B6) genetic background, making it a useful new tool for understanding the pathophysiology of atherosclerosis and for evaluating additional genetic modifiers regulating hyperlipidemia and atherogenesis. Further investigation of genomic differences between the ENU mutant and KO strains may reveal previously unappreciated sequence functionality.
Recommended Citation
Svenson KL,
Ahituv N,
Durgin RS,
Savage H,
Magnani PA,
Foreman O,
Paigen B,
Peters LL.
A new mouse mutant for the LDL receptor identified using ENU mutagenesis. J Lipid Res 2008 Nov; 49(11):2452-62.