Overview

Also Known As:hAbeta/APOE3

hAbeta/APOE3 mice carry an R130C mutation in the Apoe^{tm1.1(APOE*4)Adiuj} allele (Stock No. 027894) that expresses the human APOE isoform E3 (APOE3 KI), and a CRISPR/Cas9-generated App allele with a humanized Abeta1-42 region (G601R, F606Y, R609H in the mouse gene, corresponding to amino acid positions 676, 681, 684 in the human APP locus). These mice may be suitable for use in studies related to Alzheimer's disease, lipoproteins, arteriosclerosis, and coronary heart disease.

Donating Investigator

Mike Sasner, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

App^em1Adiuj

Allele Type	Gene Symbol	Gene Name
Endonuclease-mediated (Humanized sequence)	App	amyloid beta (A4) precursor protein

Apoe^{em2(APOE)Adiuj}*

Allele Type	Gene Symbol	Gene Name
Endonuclease-mediated (Inserted expressed sequence, Humanized sequence)	Apoe	apolipoprotein E

View Genetics

Research Applications

Metabolism Research
Neurobiology Research
Research Tools
Cardiovascular Research

View All Research Applications

Details

Detailed Description

hAbeta/APOE3 mice carry an R130C mutation in the Apoe^{tm1.1(APOE*4)Adiuj} allele (Stock No. 027894) that expresses the human APOE isoform E3 (APOE3 KI), and a CRISPR/Cas9-generated App allele with a humanized Abeta1-42 region (G601R, F606Y, R609H in the mouse gene, corresponding to amino acid positions 676, 681, 684 in the human APP locus). These mice may be suitable for use in studies related to Alzheimer's disease, lipoproteins, arteriosclerosis, and coronary heart disease.

Development

Apoe^{em2(APOE*)Adiuj} - see Stock No. 029018
To generate this APOE3 KI, a mutagenic oligo based approach was used. Plasmids encoding a signal guide RNA designed to introduce a R130C point mutation into the Apoe^{tm1.1(APOE*4)Adiuj} allele (Stock No. 027894) and the cas9 nuclease were introduced into the cytoplasm-derived fertilized eggs with well recognized pronuclei. Resultant mice were identified by sequencing and PCR and further bred to C57BL/6J (Stock No. 000664) to develop the colony.

App^em1Adiuj - see Stock No. 030670
Plasmids encoding a single guide RNA designed to introduce the G601R, F606Y, and R609H point mutations into the App gene and the cas9 nuclease were introduced into the cytoplasm of Stock No. 028709-derived fertilized eggs with well recognized pronuclei. G601R corresponds to a GGA to CGA nucleotide change, F606Y represents a TTT to TAT nucleotide mutation, and R609H incorporates a CGC to CAT nucleotide change. The Apoe^{tm1.1(APOE*4)Adiuj} and Trem2^em1Adiuj mutations were bred away.

Important note about App isoforms and exon numbering: The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16.

Expression Data

Expressed Gene	APOE, apolipoprotein E, human
Site of Expression

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

App^em1Adiuj

Allele Symbol: App^em1Adiuj

Allele Name	endonuclease-mediated mutation 1, MODEL-AD Center
Allele Type	Endonuclease-mediated (Humanized sequence)
Allele Synonym(s)
Gene Symbol and Name	App, amyloid beta (A4) precursor protein
Gene Synonym(s)
Strain of Origin	B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J
Chromosome	16
Molecular Note	CRISPR/Cas9 genome editing methodologies are used to introduce G601R, F606Y, and R609H point mutations into the App gene. G601R corresponds to a GGA to CGA nucleotide change, F606Y represents a TTT to TAT change, and R609H incorporates a CGC to CAT nucleotide change.

Apoe^{em2(APOE)Adiuj}*

Allele Symbol: Apoe^{em2(APOE)Adiuj}*

Allele Name	endonuclease-mediated mutation 1, MODEL-AD Center
Allele Type	Endonuclease-mediated (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)
Gene Symbol and Name	Apoe, apolipoprotein E
Gene Synonym(s)
Expressed Gene	APOE, apolipoprotein E, human
Strain of Origin	B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}/J
Chromosome	7
Molecular Note	CRISPR-Cas9 methodology introduced a R130C point mutation into the human APOE protein carried by the Apoe^{tm1.1(APOE*4)Adpmc} allele.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Metabolism Research
- Lipid Metabolism
Neurobiology Research
- Alzheimer's Disease
  - APP mutants
  - APOE mutants
Research Tools
- Cardiovascular Research
- Neurobiology Research
Cardiovascular Research

Mammalian Phenotype Terms by Genotype

References

Additional - Apoe^{em2(APOE)Adiuj}* related

Additional - App^em1Adiuj related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Apoe
- Probe:Apoe 5' CT Alternate1
- Probe:App (G601R) Probe
- Probe:Apoe-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

Compound heterozygotes and homozygotes are viable and fertile.
- Additional Breeding and Husbandry Support
Citation
When using the hAbeta/APOE3 mouse strain in a publication, please cite the originating article(s) and include JAX stock #034455 in your Materials and Methods section.

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Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

The use of this mouse model is subject to the terms and conditions of the Limited License from The Broad Institute.

The use of this mouse model is subject to the terms and conditions of the Limited Use Label License from Caribou Biosciences, Inc.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

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Also Known As:hAbeta/APOE3

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Appem1Adiuj

Allele Symbol: Appem1Adiuj

Apoeem2(APOE*)Adiuj

Allele Symbol: Apoeem2(APOE*)Adiuj

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Apoeem2(APOE*)Adiuj related

Additional - Appem1Adiuj related

Genotyping Protocols

Breeding Considerations

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

App^em1Adiuj

Allele Symbol: App^em1Adiuj

Apoe^{em2(APOE)Adiuj}*

Allele Symbol: Apoe^{em2(APOE)Adiuj}*

Additional - Apoe^{em2(APOE)Adiuj}* related

Additional - App^em1Adiuj related