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Strain Name:

B6.Cg-Tg(GFAP-APOE*4)1Hol Apoetm1Unc/J

Stock Number:

004631

Availability:

Repository- Live

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Former Name      B6.Cg-Tg(GFAP-APOE4)1Hol Apoetm1Unc/J    (Changed: 11-JUL-07 )
Genes & Alleles   APOE;   Apoe;   Apoetm1Unc;   GFAP;   Tg(GFAP-APOE*4)1Hol;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Type JAX® GEMM® Strain - Transgenic
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator David Holtzman,   Washington University
GenerationN6F?+1N1F6N1F5 (27-APR-08)

Strain 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 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.

Strain 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.

Mammalian Phenotype Terms assigned by genotype

Apoetm1Unc/Apoetm1Unc Tg(GFAP-APOE*4)1Hol/0

        B6.Cg-Tg(GFAP-APOE*4)1Hol Apoetm1Unc/J
  • nervous system phenotype
  • abnormal glial cell physiology (MGI Ref ID J:58019)
    • the ratio of lipid to Apoe in HDL particles secreted from astrocytes is lower than in wild type astrocytes but higher than in Apoetm1Unc homozygotes

Gene & Allele Details

Allele Symbol Apoetm1Unc
Allele Name targeted mutation 1, University of North Carolina
Common Name(s) APOE KO; AopE(-); ApoE-KO; Apoetm1Un; apoE-; apoE0; epsilon-;
Mutation Made By Nobuyo Maeda,   Univ of North Carolina at Chapel Hill
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Apoe, apolipoprotein E
Chromosome 7
Gene Common Name(s) AD2; AI255918; APOEA; LPG; MGC1571; apoprotein; expressed sequence AI255918;
General Note

In Apoetm1Unc mutant mice also carrying Csf1op, atherotic lesions of the proximal aorta were abolished or significantly reduced in size relative to Apoe mutants homozygous for the normal allele at Csf1 (J:40136). The results may have been due to reduced macrophages or M-CSF, but were not due to reductions in circulating lipoprotein (J:40136).

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. [MGI Ref ID J:1050]
 
Allele Symbol Tg(GFAP-APOE*4)1Hol
Allele Name transgene insertion 1, David M Holtzman
Common Name(s) GFAP-apoE4 line1; Tg(GFAP-APOE4)1Hol;
Mutation Made By David Holtzman,   Washington University
Strain of OriginC57BL/6 and CBA
Expressed Gene APOE, apolipoprotein E, human
Promoter GFAP, glial fibrillary acidic protein, 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. [MGI Ref ID J:93487]

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Apoetm1Unc
Tg(GFAP-APOE*4) QPCR
Tg(GFAP-APOE*4)1Hol, Tg(GFAP-APOE*2)14Hol, Tg(GFAP-APOE*3)37Hol

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Apoetm1Unc     (9 strains)

Strains carrying other alleles of APOE
004632   B6.Cg-Tg(GFAP-APOE*2)14Hol Apoetm1Unc/J
008408   B6;D2-Tg(APOE-NPC1L1)20Lqyu/J
007744   C57BL/6-Tg(APOE-DGAT2)24Far/J
003285   C57BL/6-Tg(LIPC)6784His/J
View Strains carrying other alleles of APOE     (4 strains)

View Strains carrying other alleles of GFAP     (8 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Animal Health Reports

Room Number           AX12

Research Applications

This mouse can be used to support research in many areas including:

Apoetm1Unc related

Cardiovascular Research
Atherosclerosis
Hypercholesterolemia

Mouse/Human Gene Homologs
Alzheimer's
hyperlipoproteinemia, type III

Tg(GFAP-APOE*4)1Hol related

Neurobiology Research
Alzheimer's Disease (APOE mutants)

References

Selected Reference(s)

Sun Y; Wu S; Bu G; Onifade MK; Patel SN; LaDu MJ; Fagan AM; Holtzman DM. 1998. Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins. J Neurosci 18(9):3261-72. [PubMed: 9547235]  [MGI Ref ID J:93487]

Additional References

Price and Supply Information

Strain Name: B6.Cg-Tg(GFAP-APOE*4)1Hol Apoetm1Unc/J
Stock Number: 004631

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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