title: A new mouse mutant for the LDL receptor identified using ENU mutagenesis.
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.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA. ksven@jax.org
authors.forename: Karen L
authors.initials: KL
authors.lastname: Svenson
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Durgin
authors.forename: Holly
authors.initials: H
authors.lastname: Savage
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Magnani
authors.forename: Oded
authors.initials: O
authors.lastname: Foreman
authors.forename: Beverly
authors.initials: B
authors.lastname: Paigen
authors.forename: Luanne L
authors.initials: LL
authors.lastname: Peters
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000008:administration & dosage*; D005260:Female; D006938:Hyperlipoproteinemia Type II / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics*; D009153:Mutagens / Q000008:administration & dosage*; D020125:Mutation, Missense / Q000235:genetics*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*
chemical_list: D009153:Mutagens; D011973:Receptors, LDL; D005038:Ethylnitrosourea