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 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
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.
|Expressed Gene||APOE, apolipoprotein E, human|
|Site of Expression|
|Site of Expression|
|Allele Name||transgene insertion 1, David M Holtzman|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||transgene insertion 1, David M Holtzman; Cdh18Tg(GFAP-APOE_i4)1Hol|
|Gene Symbol and Name||Cdh18, cadherin 18|
|Gene Synonym(s)||B230220E17Rik; CDH14; B230220E17Rik; CDH14L; CDH24; RIKEN cDNA B230220E17 gene|
|Promoter||GFAP, glial fibrillary acidic protein, human|
|Expressed Gene||APOE, apolipoprotein E, human|
|Strain of Origin||C57BL/6 or 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. 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.|
|Mutations Made By|| |
Dr. David Holtzman, Washington University
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, University of North Carolina; Apoetm1Unc|
|Gene Symbol and Name||Apoe, apolipoprotein E|
|Gene Synonym(s)||expressed sequence AI255918; APO-E; AD2; LPG; AI255918; LDLCQ5; APOEA; ApoE4|
|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
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>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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