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Strain Name:

B6.Cg-Tg(GFAP-APOE*2)14Hol Apoetm1Unc/J

Stock Number:

004632

Availability:

Repository-Cryopreserved

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Genes & Alleles   APOE;   Apoe;   Apoetm1Unc;   GFAP;   Tg(GFAP-APOE*2)14Hol;

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
Specieslaboratory mouse
Donating Investigator David Holtzman,   Washington University

Strain Description
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.

Strain Development
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.

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. [J:1050]
 
Allele Symbol Tg(GFAP-APOE*2)14Hol
Allele Name transgene insertion 14, David M Holtzman
Common Name(s) GFAP-apoE2 line14; Tg(GFAP-APOE2)14Hol;
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
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. [J:93487]

Control Information

  Allele   Control
 Apoetm1Unc  000664 C57BL/6J (approximate)
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Genotyping Protocols

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

Colony Maintenance

Breeding & HusbandryThe resulting transgenic founder animals were bred to B6.129P2-Apoetm1Unc (Stock #: 2052) for ten generations.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Apoetm1Unc     (9 strains)

Strains carrying other alleles of APOE
004631   B6.Cg-Tg(GFAP-APOE*4)1Hol Apoetm1Unc/J
007744   C57BL/6-Tg(APOE-DGAT2)24Far/J
003285   C57BL/6-Tg(LIPC)6784His/J
View Strains carrying other alleles of APOE     (3 strains)

View Strains carrying other alleles of GFAP     (7 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.

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*2)14Hol 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]  [J:93487]

Additional References

Price and Supply Information

Strain Name: B6.Cg-Tg(GFAP-APOE*2)14Hol Apoetm1Unc/J
Stock Number: 004632

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to the Supply Notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
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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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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