B6.Cg-Apoe^tm1Unc Cdh18^{Tg(GFAP-APOE_i4)1Hol}/J

Stock number: 004631
Product name: GFAP-apoE4
Strain synonyms: Tg(GFAP-APOE*4)1Hol
Research areas: Cardiovascular Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These transgenic mice express the human apolipoprotein E4 isoform (APOE4) under the direction of the human glial fibrillary acidic protein (GFAP) promoter and do not express endogenous mouse apolipoprotein E (APOE). Human APOE4 is detectable in glia and neuropil in developing and adult mutant mice. This mutant mouse strain represents a model that may be useful in studies examining the function of APOE4 in the central nervous system and how APOE4 may contribute to the pathology of Alzheimer's disease.

Detailed description

These transgenic mice express the human apolipoprotein E4 isoform (APOE4) under the direction of the human glial fibrillary acidic protein (GFAP) promoter and do not express endogenous mouse apolipoprotein E (Apoe). The transgene integrated into chromosome 15 causing an 8648 bp deletion in Cdh18 (cadherin 18). Founder line 1 has a copy number of 10-15. The transgenic isoform expression pattern follows the endogenous mouse Apoe and GFAP expression patterns in the brain. Human APOE4 is immunodetectable in glia and neuropil in developing and adult mutant mice. Cultured astrocytes from transgenic mice secrete APOE4 in lipoproteins that are similar in size to high-density (HDL) plasma lipoproteins. Detergent-soluble APOE4 protein levels in hemizygous mice forebrain tissue and in adult human cortex tissue are similar. Mice that are hemizygous or homozygous for the transgenic insert and homozygous for the targeted allele are viable, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain represents a model that may be useful in studies examining the function of APOE4 in the central nervous system and how APOE4 may contribute to the pathology of Alzheimer's disease.

According to the donating investigator, mice that are hemizygous for the transgene and homozygous for the null mutation show dyslipidemia similar to non-transgenic Apoe-null mutant mice (B6.129P2-Apoe/J - Stock # 002052) in peripheral blood. Although some transgene-derived APOE protein does make it to the periphery, it is not enough to lower peripheral cholesterol significantly.

Development

A transgenic construct containing sequence encoding human apolipoprotein E4 isoform under the control of the human glial fibrillary acidic protein (GFAP) promoter was introduced into B6;CBA donor eggs. The transgene integrated into chromosome 15 causing an 8648 bp deletion in Cdh18 (cadherin 18). Founder line 1 has a copy number of 10-15.

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.

Allele

Symbol: Cdh18^{Tg(GFAP-APOE_i4)1Hol}
Name: transgene insertion 1, David M Holtzman
MGI accession ID: MGI:3057182
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Cdh18
Marker name: cadherin 18
Chromosome: 15
Strain of origin: C57BL/6 or CBA
Expressed genes: APOE,apolipoprotein E,human
Molecular note: The transgene contains sequence encoding human apolipoprotein E4 isoform under the control of the human glial fibrillary acidic protein (GFAP) promoter. Five lines were created (lines 1, 3, 11, 19 and 22) with line 1 being chosen as the representative line based on submission to the Jax repository. The pattern of expression of the human apolipoprotein E3 isoform (APOE3) transgenic product in these mice follows the endogenous mouse APOE and GFAP expression patterns in the brain. Human APOE3 is immunodetectable in glia and neuropil in developing and adult mutant mice. Line 1 inserted into coordinates 23364633-23373281 (Build GRCm38/mm10) resulting in an 8648 bp deletion. Founder line 1 has a copy number of 10-15.