B6.129S(Cg)-Apoe^{tm1(APOE*)Ljohn}/J

Stock number: 034676
Product name: APOE switch , 4s2
Research areas: Neurobiology Research

Description

APOE switch mice (4s2) have human APOE4 exons 2-4 replacing mouse exons 2-4 of the Apoe (apoliprotein E) gene. In addition, human exon 4 and a stop codon are flanked by loxP sites followed by exon 4 from the APOE2 isoform, providing a conditional "switch". This strain may be useful in studying Alzheimer's disease and related phenotypes.

Detailed description

Apoe (apoliprotein E) encodes a fat-binding protein involved lipoprotein metabolism and cardiovascular disease. It is involved in the transport of fats, fat-soluble vitamin, cholesterol into the lymph system. In humans, the APOE4 isoform is associated with highest risk of Alzheimer's disease with the earliest onset in certain populations. One copy of the allele is found in 15 to 25% of people. The APOE2 isoform has the lowest risk of Alzheimer's disease, and those that do develop Alzheimer's do so later in life. One copy of the APOE2 allele is found in 5-10% of people.

APOE switch mice (4s2) have human APOE4 exons 2-4 replacing mouse exons 2-4 of the Apoe gene. In addition, human exon 4 and a stop codon are flanked by loxP sites followed by exon 4 from the APOE2 isoform, providing a conditional "switch". The donating investigator indicates that phenotype of the APOE switch mice (4s2) prior to Cre recombination is similar to mice carrying the Apoe^{tm3(APOE*4)Mae} allele. Cre-mediated recombination removes human exon 4 and allows transcription of human APOE2 exon 4. Characterization of the strain is ongoing and will be updated (August 2023).

Development

APOE switch mice (4s2) were generated on a 129S6/SvEv background at TransViragen Inc (Chapel Hill, NC). Human APOE exons 2-4 were inserted into the mouse Apoe genomic sequence. The coding region of APOE (Exon 4) and a stop codon is flanked by loxP sites. Following the stop codon is an additional exon 4 containing the sequence for APOE2. The construct was electroporated into 129S/SvEv-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeras were bred with C57BL/6N  mice and mice were then crossed to Aldh1l1-CreERT2 mice on a C57BL/6 congenic background. The cre allele was later bred out. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304), mice were then backcrossed for an additional 3 generations.

Allele

Symbol: Apoe^{tm1(APOE*)Ljohn}
Name: targeted mutation 1, Lance Johnson
MGI accession ID: MGI:7562448
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Humanized sequence
Synonyms: 4s2; APOE switch; APOE4s2^loxP
Marker symbol: Apoe
Marker name: apolipoprotein E
Marker synonyms: AD2; APO-E; ApoE4; APOEA; LDLCQ5; LPG
Chromosome: 7
Strain of origin: 129S/SvEv
Molecular note: Human APOE exons 2-4 were inserted into the mouse Apoe genomic sequence replacing mouse exons 2-4. In addition, human exon 4 and a stop codon are flanked by loxP sites followed by exon 4 from the APOE2 isoform, providing a conditional "switch".