Overview

Also Known As:Plcg2M28L/hAbeta/APOE4/Trem2R47H

Plcg2*M28L/hAbeta/APOE4/Trem2*R47H mice express a CRISPR/Cas9-generated mutant of the phospholipase C, gamma 2 gene carrying the M28L missense mutation associated with increased risk of Alzheimer's disease.
This mutation is maintained with the hAbeta/APOE4/Trem2*R47H mutations (Stock No. 030670) intended to increase risk of late-onset Alzheimer's disease: a humanized Apoe knock-in mutation (sequence coding for human isoform E4), 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) and a CRISPR/Cas9-generated R47H point mutation of the Trem2 gene.

Donating Investigator

Mike Sasner, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Trem2^em1Adiuj

Allele Type	Gene Symbol	Gene Name
Endonuclease-mediated (Humanized sequence)	Trem2	triggering receptor expressed on myeloid cells 2

Apoe^{tm1.1(APOE4)Adiuj}*

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence, Humanized sequence)	Apoe	apolipoprotein E

App^em1Adiuj

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

Plcg2^em3Adiuj

Allele Type	Gene Symbol	Gene Name
Endonuclease-mediated (Humanized sequence)	Plcg2	phospholipase C, gamma 2

View Genetics

Research Applications

Metabolism Research
Neurobiology Research
Research Tools
Cardiovascular Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

This quadruple mutant strain incorporates a humanized Apoe knock-in mutation (sequence coding for isoform E4), a CRISPR/Cas9 generated mutant of the Plcg2 gene with the M28L mutation, CRISPR/cas9-generated G601R, F606Y, and R609H mutations of the App gene, and a CRISPR/Cas9-generated R47H point mutation of the Trem2 gene. These mice may be suitable for use in studies related to Alzheimer's disease, lipoproteins, arteriosclerosis, and coronary heart disease.

The viability/fertility of Plcg2^em3Adiuj homozygotes has not been assessed (February, 2020).

Development

The following mutations were intercrossed:

Apoe^{tm1.1(APOE*4)Adiuj} - see Stock No. 027894

Plcg2^em3Adiuj - see Stock No. 030674

App^em1Adiuj - see Stock No. 030670

Trem2^em1Adiuj - see Stock No. 027918

Expression Data

Expressed Gene	APOE, apolipoprotein E, human
Site of Expression	Endogenous mouse elements direct human APOE gene sequence (including exons 2, 3 and 4 and some 3' UTR sequence).
Site of Expression
Site of Expression

Control Suggestions

030670 B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj} App^em1Adiuj Trem2^em1Adiuj/J

Additional Information

Considerations for Choosing Controls

Genetics

Trem2^em1Adiuj

Allele Symbol: Trem2^em1Adiuj

Allele Name	endonuclease-mediated mutation 1, MODEL-AD Center
Allele Type	Endonuclease-mediated (Humanized sequence)
Allele Synonym(s)	Jax R27H ki; Trem2 R47H KI
Gene Symbol and Name	Trem2, triggering receptor expressed on myeloid cells 2
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	17
Molecular Note	The allele was generated by injecting cas9 nuclease and a single guide RNA designed to introduce a R47H point mutation with two silent mutations (lysine AAG>AAA and alanine GCC>GCA) into the gene.

Apoe^{tm1.1(APOE4)Adiuj}*

Allele Symbol: Apoe^{tm1.1(APOE4)Adiuj}*

Allele Name	targeted mutation 1.1, MODEL-AD Center
Allele Type	Targeted (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	APOE^epsilon4
Gene Symbol and Name	Apoe, apolipoprotein E
Gene Synonym(s)
Expressed Gene	APOE, apolipoprotein E, human
Site of Expression	Endogenous mouse elements direct human APOE gene sequence (including exons 2, 3 and 4 and some 3' UTR sequence).
Strain of Origin	C57BL/6J
Chromosome	7
Molecular Note	The targeting vector contains a 3' FRT flanked neo cassette and 1.5 kb of human APOE gene sequence including exons 2, 3, 4 and a portion of the 3'UTR sequence (the APOE4 isoform) which is used to replace exons 2, 3 and most of exon 4 of the endogenous sequence. The human ApoE sequence carries a 2 nucleotide A to T substitution in intron 3. Flp-mediated recombination removed the FRT-flanked neo cassette.

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.

Plcg2^em3Adiuj

Allele Symbol: Plcg2^em3Adiuj

Allele Name	endonuclease-mediated mutation 3, MODEL-AD Center
Allele Type	Endonuclease-mediated (Humanized sequence)
Allele Synonym(s)
Gene Symbol and Name	Plcg2, phospholipase C, gamma 2
Gene Synonym(s)
Strain of Origin	B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J
Chromosome	8
Molecular Note	The allele was generated by injecting cas9 nuclease and a single guide RNA designed to introduce a M28L point mutation.

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
  - APOE mutants
  - APP mutants
Research Tools
- Cardiovascular Research
- Neurobiology Research
Cardiovascular Research

Mammalian Phenotype Terms by Genotype

References

Additional - Apoe^{tm1.1(APOE4)Adiuj}* related

Additional - App^em1Adiuj related

Additional - Plcg2^em3Adiuj related

Additional - Trem2^em1Adiuj related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Trem2
- Standard PCR:Apoe
- Standard PCR:Apoe
- Probe:App
- End Point Analysis:Plcg2
- Probe:Apoe-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

The viability/fertility of Plcg2^em3Adiuj homozygotes has not been assessed (February, 2020).
Intercrossing animals homozygous for Apoe^{tm1.1(APOE*4)Adiuj}, Trem2^em1Adiuj, and App^em1Adiuj, and heterozygous for Plcg2^em3Adiuj with animals that are homozygous for Apoe^{tm1.1(APOE*4)Adiuj}, Trem2^em1Adiuj, and App^em1Adiuj, and wildtype for Plcg2^em3Adiuj is currently recommended.
- Additional Breeding and Husbandry Support
Mating System
- homozygous for Apoe^{tm1.1(APOE*4)Adiuj} heterozygous for Plcg2^em3Adiuj homozygous for App^em1Adiuj homozygous Trem2^em1Adiuj
- X homozygous for Apoe^{tm1.1(APOE*4)Adiuj} wildtype for Plcg2^em3Adiuj homozygous for App^em1Adiuj homozygous Trem2^em1Adiuj
  OR
  homozygous for Apoe^{tm1.1(APOE*4)Adiuj} wildtype for Plcg2^em3Adiuj homozygous for App^em1Adiuj homozygous Trem2^em1Adiuj
- X homozygous for Apoe^{tm1.1(APOE*4)Adiuj} heterozygous for Plcg2^em3Adiuj homozygous for App^em1Adiuj homozygous Trem2^em1Adiuj
Citation
When using the Plcg2*M28L/hAbeta/APOE4/Trem2*R47H mouse strain in a publication, please cite the originating article(s) and include JAX stock #034454 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
> >	Homozygous for Apoe<tm1.1(APOE*4)Adiuj>, heterozygous or wildtype for Plcg2<em3Adiuj>, homozygous or heterozygous for App<em1Adiuj>, and homozygous for Trem2<em1Adiuj>

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

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

Also Known As:Plcg2*M28L/hAbeta/APOE4/Trem2*R47H

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Trem2em1Adiuj

Allele Symbol: Trem2em1Adiuj

Apoetm1.1(APOE*4)Adiuj

Allele Symbol: Apoetm1.1(APOE*4)Adiuj

Appem1Adiuj

Allele Symbol: Appem1Adiuj

Plcg2em3Adiuj

Allele Symbol: Plcg2em3Adiuj

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 - Apoetm1.1(APOE*4)Adiuj related

Additional - Appem1Adiuj related

Additional - Plcg2em3Adiuj related

Additional - Trem2em1Adiuj related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:Plcg2M28L/hAbeta/APOE4/Trem2R47H

Trem2^em1Adiuj

Allele Symbol: Trem2^em1Adiuj

Apoe^{tm1.1(APOE4)Adiuj}*

Allele Symbol: Apoe^{tm1.1(APOE4)Adiuj}*

App^em1Adiuj

Allele Symbol: App^em1Adiuj

Plcg2^em3Adiuj

Allele Symbol: Plcg2^em3Adiuj

Additional - Apoe^{tm1.1(APOE4)Adiuj}* related

Additional - App^em1Adiuj related

Additional - Plcg2^em3Adiuj related

Additional - Trem2^em1Adiuj related