These GFAP-apoE2 line14 mice express a transgene containing human APOE2 and follows the endogenous mouse APOE and GFAP expression patterns in the brain.
Dr. David M. Holtzman, Washington University
These transgenic mice express the human apolipoprotein E2 isoform (APOE2) 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 APOE2 is immunodetectable in glia and neuropil in developing and adult mutant mice. Cultured astrocytes from transgenic mice secrete APOE2 in lipoproteins that are similar in size to high-density (HDL) plasma lipoproteins. Detergent-soluble APOE2 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 APOE2 in the central nervous system and how APOE2 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 E2 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|
|General Note||Phenotypic Similarity to Human Syndrome: Coronary Artery Disease (CAD) in mice homozygous for Apoe tm1Unc and Scarb1 tm1Kri on a mixed 129, BALB/c and C57BL/6 background (J:201999) |
Phenotypic Similarity to Human Syndrome: Metabolic Syndrome in mice homozygous for Apoetm1Unc and Cyp19a1tm1Esi (J:184647)
Phenotypic Similarity to Human Syndrome: Metabolic Syndrome in mice homozygous for Apoetm1Unc and heterozygous for Ay and a (J:177084)
|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 14, David M Holtzman|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||GFAP-apoE2 line14; Tg(GFAP-APOE*2)14Hol; Tg(GFAP-APOE2)14Hol|
|Gene Symbol and Name||Tg(GFAP-APOE_i2)14Hol, transgene insertion 14, David M Holtzman|
|Gene Synonym(s)||GFAP-apoE2 line14; Tg(GFAP-APOE*2)14Hol; Tg(GFAP-APOE*2)14Hol; Tg(GFAP-APOE2)14Hol; Tg(GFAP-APOE2)14Hol|
|Promoter||GFAP, glial fibrillary acidic protein, human|
|Expressed Gene||APOE, apolipoprotein E, human|
|Strain of Origin||C57BL/6 and CBA|
|General Note||Transgenic mice do not express endogenous mouse apolipoprotein E (APOE). The expression pattern of the transgenic human apolipoprotein E2 isoform (APOE2) follows the endogenous mouse APOE and GFAP expression patterns in the brain. Human APOE2 is immunodetectable in glia and neuropil in developing and adult mutant mice. Cultured astrocytes from transgenic mice secrete APOE2 in lipoproteins that are similar in size to high density plasma lipoproteins (HDL). Detergent-soluble APOE2 protein levels in forebrain tissue from hemizygous mice and in adult human cortex tissue are similar. |
Mice that are hemizygous or homozygous for the transgenic insert and homozygous for Apoetm1Unc are viable, normal in size, and do not display any gross physical or behavioral abnormalities.
|Molecular Note||The transgene contains sequence encoding human apolipoprotein E2 isoform under the control of the human glial fibrillary acidic protein (GFAP) promoter.|
|Mutations Made By|| |
Dr. David Holtzman, Washington University
The resulting transgenic founder animals were bred to B6.129P2-Apoetm1Unc (Stock #: 2052) for ten generations.
|Please inquire about possible genotypes.|
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