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.
Dr. David M. Holtzman, Washington University
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 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
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.
|Expressed Gene||APOE, apolipoprotein E, human|
|Site of Expression|
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||APOE KO; AopE(-); ApoE-KO; Apoetm1Un; EKO; apoE-; apoE0; epsilon-; mE-; mEKO|
|Gene Symbol and Name||Apoe, apolipoprotein E|
|Gene Synonym(s)||AD2; AI255918; APO-E; APOEA; ApoE4; LDLCQ5; LPG; expressed sequence AI255918|
|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.|
|Mutations Made By|| |
Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill
|Allele Name||transgene insertion 1, David M Holtzman|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||GFAP-apoE4 line1; Tg(GFAP-APOE*4)1Hol; Tg(GFAP-APOE4)1Hol|
|Gene Symbol and Name||Tg(GFAP-APOE_i4)1Hol, transgene insertion 1, David M Holtzman|
|Gene Synonym(s)||GFAP-apoE4 line1; Tg(GFAP-APOE*4)1Hol; Tg(GFAP-APOE*4)1Hol; Tg(GFAP-APOE4)1Hol; Tg(GFAP-APOE4)1Hol|
|Promoter||GFAP, glial fibrillary acidic protein, human|
|Expressed Gene||APOE, apolipoprotein E, human|
|Strain of Origin||C57BL/6 and CBA|
|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.|
|Mutations Made By|| |
Dr. David Holtzman, Washington University
When using the GFAP-apoE4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #004631 in your Materials and Methods section.
|Homozygous for Tg(GFAP-APOE*4)1Hol ,Homozygous for Apoe<tm1Unc>|
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