Submitted on June 6, 2008
Revised on July 11, 2008
Accepted on July 14, 2008
A new mouse mutant for the LDL receptor identified using ENU mutagenesis
Karen L. Svenson, Nadav Ahituv, Rebecca S. Durgin, Holly Savage, Phyllis A. Magnani, Oded Foreman, Beverly Paigen, and Luanne L. Peters
The Jackson Laboratory, Bar Harbor, ME 04609
Corresponding Author: ksven{at}jax.org
In an effort to discover new mouse models of cardiovascular disease using 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 to 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.
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