Overview

Also Known As:ApoE-Flox

These floxed mutant mice possess loxP sites flanking exon 3 of the Apoe gene. This strain may be useful for generating conditional mutations in applications related to the regulation of lipoprotein and cholesterol metabolism, neurovascular function, inflammation and in the pathophysiology of neurodegenerative cardiovascular diseases.

Donating Investigator

Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill

Theodore Mazzone, NorthShore University HealthSystem/University of Chicago

Genetic overview

Genetic Background	Generation

Apoe^tm1.1Mae

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Apoe	apolipoprotein E

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Research Applications

Neurobiology Research
Cardiovascular Research
Research Tools
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

A major function of apolipoprotein E (APOE) is mediation of lipid transport throughout various tissues and cells. Circulating APOE is associated with chylomicron and Intermediate-density lipoprotein (IDLs) and is mostly produced by the liver, although other tissues and cells, including adrenal gland, macrophages, vascular smooth muscle cells, and adipocytes, are also known to synthesize and secrete APOE.
In the central nervous system, APOE is produced by glial cells, and by injured neurons and cells in the choroid plexus at a lower levels than observed in astrocytes. APOE is important in lipoprotein and cholesterol metabolism, neurovascular function, regulation of the immune system and in the pathophysiology of neurodegenerative diseases such as Alzheimer’s disease and cardiovascular diseases such as atherosclerosis.
These mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues.
Removal of the floxed sequence creates a null allele.

When bred to a strain with Cre recombinase expression in adipose tissue (see Stock No. 005069 for example) to generate SEKO (selective apoE knockout- adipose tissue) mice, this mutant mouse strain may be useful in studies of lipid metabolism and adipose tissue inflammation.

Development

A targeting vector designed by Drs. Theodore Mazzone (University of Chicago) and Nobuyo Maeda (University of North Carolina, Chapel Hill) containing a FRT site flanked NEO cassette was utilized in the construction of this mutant. This selection cassette and a loxP site was inserted downstream of exon 3 of the targeted gene, and another loxP site was inserted upstream of exon 3. This construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells which were transiently transfected with a FLP recombinase vector to remove the selection cassette. ES cells that had successfully undergone FLP recombination and no longer retained the selection cassette but did retain the loxP-flanked exon 3 were injected in blastocysts. The resulting chimeric animals were tested for germline transmission.
The mice were then backcrossed to C57BL/6J for 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Huang ZH; Reardon CA; Getz GS; Maeda N; Mazzone T. 2015. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation. J Lipid Res 56(2):215-26PubMed: 25421060 MGI: J:219838

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Genetics

Apoe^tm1.1Mae

Allele Symbol: Apoe^tm1.1Mae

Allele Name	targeted mutation 1.1, Nobuyo Maeda
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Apoe^flox
Gene Symbol and Name	Apoe, apolipoprotein E
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	7
Molecular Note	The targeting vector contains a loxP site and an FRT-flanked neo cassette inserted downstream of exon 3 of the targeted gene, and another loxP site inserted upstream of exon 3. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 3 floxed.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Alzheimer's Disease
- Cre-lox System
  - loxP-flanked Sequences
Cardiovascular Research
- Atherosclerosis
Research Tools
- Diabetes and Obesity Research
  - loxP
- Cre-lox System
  - loxP-flanked Sequences
Metabolism Research
- Lipid Metabolism

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Apoe^tm1.1Mae/Apoe^tm1.1Mae Tg(Fabp4-cre)1Rev/0
B6.Cg-Apoe Tg(Fabp4-cre)1Rev

homeostasis/metabolism phenotype

decreased liver cholesterol level

increased cholesterol level
- increased cholesterol level in skeletal muscle

decreased circulating glucose level

decreased circulating insulin level

decreased liver triglyceride level

improved glucose tolerance

decreased circulating cholesterol level
- reduced plasma total cholesterol

decreased triglyceride level
- decreased triglyceride level in white adipose tissue, heart and muscle

increased insulin sensitivity
- reduced HOMA-IR

decreased cholesterol level
- decreased cholesterol level in white adipose tissue and heart

decreased circulating triglyceride level
- reduced plasma triglyceride at 12-13 weeks, but not 8 weeks

immune system phenotype

decreased macrophage cell number
- numbers of inflammatory adipose tissue macrophages (M1) are decreased, although total number is similar to control

increased macrophage cell number
- numbers of non-inflammatory adipose tissue macrophage (M2) are increased, although total number is similar to controls

adipose tissue phenotype

decreased epididymal fat pad weight
- ratio of epididymal fat pad weight to body weight is reduced
- adipocyte number is not decreased, however, adipocyte size and lipid content is reduced

decreased white fat cell size
- reduced adipocyte volume

decreased white fat cell lipid droplet size

liver/biliary system phenotype

decreased liver cholesterol level

decreased liver triglyceride level

hematopoietic system phenotype

decreased macrophage cell number
- numbers of inflammatory adipose tissue macrophages (M1) are decreased, although total number is similar to control

increased macrophage cell number
- numbers of non-inflammatory adipose tissue macrophage (M2) are increased, although total number is similar to controls

References

Huang ZH; Reardon CA; Getz GS; Maeda N; Mazzone T. 2015. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation. J Lipid Res 56(2):215-26PubMed: 25421060 MGI: J:219838

Additional - Apoe^tm1.1Mae related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Apoe
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the ApoE-Flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #028530 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Apoe<tm1.1Mae>

Related Products and Services

Frozen Mouse Embryo	B6.129S6-Apoe<tm1.1Mae>/MazzJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S6-Apoe<tm1.1Mae>/MazzJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S6-Apoe<tm1.1Mae>/MazzJ Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S6-Apoe<tm1.1Mae>/MazzJ Frozen Embryo	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:ApoE-Flox

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Apoetm1.1Mae

Allele Symbol: Apoetm1.1Mae

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Apoetm1.1Mae/Apoetm1.1Mae Tg(Fabp4-cre)1Rev/0B6.Cg-Apoe Tg(Fabp4-cre)1Rev

homeostasis/metabolism phenotype

immune system phenotype

adipose tissue phenotype

liver/biliary system phenotype

hematopoietic system phenotype

References

Additional - Apoetm1.1Mae related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Apoe^tm1.1Mae

Allele Symbol: Apoe^tm1.1Mae

Genotype: Apoe^tm1.1Mae/Apoe^tm1.1Mae Tg(Fabp4-cre)1Rev/0
B6.Cg-Apoe Tg(Fabp4-cre)1Rev

Additional - Apoe^tm1.1Mae related