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Strain Name:

B6.Cg-Tg(GFAP-APOE*3)37Hol Apoetm1Unc/J

Stock Number:

004633

Availability:

Repository- Live

Price and Supply Information

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Former Name      B6.Cg-Tg(GFAP-APOE3)37Hol Apoetm1Unc/J    (Changed: 11-JUL-07 )
Genes & Alleles   APOE;   Apoe;   Apoetm1Unc;   GFAP;   Tg(GFAP-APOE*3)37Hol;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
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
GenerationN10F?+6N1F5 (27-APR-08)

Strain Description
These transgenic mice express the human apolipoprotein E3 isoform (APOE3) 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 APOE3 is immunodetectable in glia and neuropil in developing and adult mutant mice. Cultured astrocytes from transgenic mice secrete APOE3 in lipoproteins that are similar in size to high-density (HDL) plasma lipoproteins. Detergent-soluble APOE3 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 APOE3 in the central nervous system and how APOE3 may contribute to the pathology of Alzheimer's disease.

Strain Development
A transgenic construct containing sequence encoding human apolipoprotein E3 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*3)37Hol/0

        B6.Cg-Tg(GFAP-APOE*3)37Hol Apoetm1Unc/J
  • nervous system phenotype
  • abnormal axon outgrowth (MGI Ref ID J:93487)
    • in vitro, neuron outgrowth is faster than in Tg(GFAP-APOE*4)22Hol Apoetm1Unc/Apoetm1Unc neurons
    • in vitro, neurite length is longer than in Tg(GFAP-APOE*4)22Hol Apoetm1Unc/Apoetm1Unc neurons
    • however, neurite outgrowth rate is equivalent to in Tg(GFAP-APOE*4)22Hol Apoetm1Unc/Apoetm1Unc neurons when neurons are treated with RAP or anti-LRP IgG
  • 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

Apoetm1Unc/Apoetm1Unc Tg(GFAP-APOE*3)37Hol/0

        B6.Cg-Apoetm1Unc Tg(GFAP-APOE*3)37Hol
  • behavior/neurological phenotype
  • abnormal fear/anxiety-related behavior (MGI Ref ID J:71062)
    • mice exhibit increased protected risk assessment behaviors in an elevated plus maze compared to wild type mice
  • abnormal locomotor activity (MGI Ref ID J:71062)
    • mice spend less time than wild type mice in the center of an open field
  • abnormal response to new environment (MGI Ref ID J:71062)
    • mice consume food slower in a new environment than Tg(GFAP-APOE*4)Hol Apoetm1Unc/Apoetm1Unc and wild type mice
    • mice require more time to habituate to a novel environment compared to wild type mice
    • mice are less reluctant than wild type mice to move into an open area
  • abnormal spatial learning (MGI Ref ID J:71062)
    • at 14 to 17 months of age, mice perform better than Tg(GFAP-APOE*4)Hol Apoetm1Unc/Apoetm1Unc and wild type mice in a rotating holeboard test
  • abnormal stationary movement (MGI Ref ID J:71062)
    • mice exhibit increased numbers of fine movement (not related to ambulation) compared to wild type mice
  • decreased startle reflex (MGI Ref ID J:71062)
    • compared to wild type mice
  • hearing/vestibular/ear phenotype
  • decreased startle reflex (MGI Ref ID J:71062)
    • compared to wild type mice

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*3)37Hol
Allele Name transgene insertion 37, David M Holtzman
Common Name(s) GFAP-apoE3 line 37; Tg(GFAP-APOE3)37Hol;
Mutation Made By David Holtzman,   Washington University
Strain of OriginC57BL/6 and CBA
Expressed Gene APOE, apolipoprotein E, pig, domestic
Promoter GFAP, glial fibrillary acidic protein, human
Molecular Note The transgene contains sequence encoding human apolipoprotein E3 isoform under the control of the human glial fibrillary acidic protein (GFAP) promoter. Two lines were created (lines 2 and 37) with line 37 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

  Allele   Control
 Apoetm1Unc  000664 C57BL/6J
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Apoetm1Unc
Tg(GFAP-APOE)
Tg(GFAP-APOE*4) QPCR

Colony Maintenance

Breeding & HusbandryThe resulting transgenic founder animals were bred to B6.129P2-Apoetm1Unc (Stock No. 002052) for ten generations.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Apoetm1Unc     (9 strains)

View Strains carrying other alleles of GFAP     (8 strains)

Additional Web Information

Congenic Nomenclature
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*3)37Hol 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*3)37Hol Apoetm1Unc/J
Stock Number: 004633

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:

*Pricing for Shipping Destination selected:

        International

Price(s) in US dollars ($)Genotype(s) Provided
Individual Mouse Price $144.20Homozygous for Tg(GFAP-APOE3)37Hol, Homozygous for Apoetm1Unc
Pair $288.40Homozygous for Tg(GFAP-APOE3)37Hol, Homozygous for Apoetm1Unc x Homozygous for Tg(GFAP-APOE3)37Hol, Homozygous for Apoetm1Unc

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 Histology and Tissue Collection Services are available for all JAX® Mice strains. For more information, please contact Customer Service at orderquest@jax.org or 1-207-288-5845.
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.
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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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