AK.129P2(B6)-Apoe^tm1Bres/SmijdJ

Stock number: 034781
Product name: apoE^-
Research areas: Cardiovascular Research

Description

This Apoe (apolipoprotein E) knock-out allele is carried on an AKR/J genetic background which is more artherosclerosis-resistant than C57BL/6J (see Stock No. 002052) and DBA/2J (see Stock No. 035010) mutation backgrounds.

Detailed description

A comparison of Apoe (apolipoprotein E) gene knock-outs on 6 different genetic backgrounds (PMID 12524234) demonstrated that genetic background contributes to arteriosclerosis susceptibility. In rank order (normalized to C57BL/6J): DBA/2J>C57BL/6J>129S4/SvJae (129/SV-ter)>AKR/J≈BALB/cByJ≈C3H/HeJ.

This Apoe knock-out allele, in which exons 1 and 2 are replaced with a neomycin cassette, is carried on an AKR/J genetic background that is more artherosclerosis-resistant than C57BL/6J (see Stock No. 002052) and DBA/2J (see Stock No. 035010) mutation backgrounds.

Apoe knock-out mice on a DBA/2J genetic background are capable of developing 10-fold larger atherosclerotic lesions than AKR/J background mice. Both DBA/2J and AKR/J background females develop larger aortic root lesions than their male counterparts.

Development

Exons 1 and 2 of the mouse Apoe gene were replaced with a neomycin resistance cassette via homologous recombination in 129P2/OlaHsd-derived E14 embryonic stem (ES) cell. The 1.4 kb deletion spans a region between a SacII site within the promoter and an XbaI site in the second intron. Resultant mice were backcrossed to C57BL/6J, then subsequently backcrossed to AKR/J for more than 15 generations by the donating laboratory.

Allele

Symbol: Apoe^tm1Bres
Name: targeted mutation 1, Jan L Breslow
MGI accession ID: MGI:2137814
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: apo E-; apoE^-; EKO; epsilon-
Marker symbol: Apoe
Marker name: apolipoprotein E
Marker synonyms: AD2; APO-E; ApoE4; APOEA; LDLCQ5; LPG
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Molecular note: A neomycin resistance cassette replaced 1.4kb of the gene, including part of the promoter through part of the second intron. Northern blot analysis using a mouse exon 4 riboprobe did not detect wild-type message in livers from homozygous mutant mice, but did detect a longer transcript that the authors propose is a neo-Apoe fusion product. Gradient SDS-PAGE analysis did not detect full size Apoe associated with any fractions from plasma lipoproteins from homozygous mutant mice.
General note:

In Apoe^tm1Bres mutant mice also carrying Csf1^op, atherotic lesions of the proximal aorta were abolished or significantly reduced in size relative to Apoe mutants homozygous for the normal allele at Csf1 (J:29024).