B6;129-Apob^tm1Sgy Apoe^tm1Unc/J

Stock number: 002878
Product name: apo-B⁴⁸ apo-E^-
Research areas: Cardiovascular Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These double Apob/Apoe knock-out mice only express APOB48 and exhibit high total and LDL cholesterol.

Detailed description

Mice homozygous for the Apob^tm1Sgy and Apoe^tm1Unc targeted mutations do not express the apolipoproteins B100 or E. They do retain the ability to express apolipoprotein B48. They have the highest total cholesterol (392 mg/dl vs 341 for Apob^tm1Unc/Apoe^tm1Unc); highest LDL cholesterol (APOB48 is not a ligand for LDLR), and atherosclerotic lesions more extensive than Apoe^tm1Unc/Apoe^tm1Unc homozygotes. The extent of atherosclerosis correlated significantly with plasma cholesterol levels.

Development

The "apo-B48-only" mice were generated using site-directed mutagenesis to introduce an oligonucleotide containing a stop codon into codon 2153 of the Apob gene. The neo resistance gene was also inserted to be used as a selectable marker. These mice were subsequently crossed to Apoe^tm1Unc mice to generate doubly knocked out mice. The Apob^tm1Sgy targeted mutation was generated in a 129 steel derived ES cell line while the Apoe^tm1Unc mutation was generated in 129P2/OlaHsd-derived E14TG2a ES cells.

Allele

Symbol: Apob^tm1Sgy
Name: targeted mutation 1, Stephen G Young
MGI accession ID: MGI:1857303
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Apob
Marker name: apolipoprotein B
Chromosome: 12
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Molecular note: A "hit and run"-type vector was used to create a stop signal in codon 2179 (codon 2153 in the original publication) in sequences corresponding to the apo-B48 editing codon. Western blot analysis on plasma derived from heterozygous and homozygous mice demostrated that the expression of the ApoB48 isoform is unaffected by this mutation, while no ApoB100 isoform is produced from this allele.
General note: Levels of LDL-cholesterol, VLDL, and triglyceride LDL are lower relative to wild-type mice in APOB48 only mice in the presence of wild-type APOE production(J:33830). APOB48 only mice have higher levels of cholesterol and more atherosclerotic lesions than APOB100 only mice in the absence of APOE (J:41510).

Allele

Symbol: Apoe^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857129
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Apoe
Marker name: apolipoprotein E
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin resistance cassette deleted part of exon 3 and part of intron 3 of the Apoe gene. Plasma from homozygous mutant mice gave no detectable immunoprecipitate by the Ouchterlony double immunodiffusion test using a rabbit antibody to rat APOE.