Overview

Also Known As: Plcg2M28L/APOE4/Trem2R47H

This triple mutant strain carries a humanized ApoE knock-in mutation (sequence coding for isoform E4), CRISPR/Cas9 generated mutant of the Plcg2 gene with the M28L mutation, 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.

Donating Investigator

Mike Sasner, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	?+pN1 (2019-01-07 00:00:00)

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

Plcg2^em3Adiuj

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

View Genetics

Research Applications

Cardiovascular Research
Research Tools
Metabolism Research
Neurobiology Research

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female

View Price List

Details

Detailed Description

This triple mutant strain carries a humanized ApoE knock-in allele, in which exons 2, 3 and most of exon 4 of the mouse Apoe gene were replaced by human APOE4 gene sequence including exons 2, 3 and 4 (and some 3' UTR sequence); a CRISPR/Cas9 generated mutant of the Plcg2, phospholipase C, gamma 2, gene with the M28L mutation; and a knock-in of a point mutation into mouse Trem2, triggering receptor expressed on myeloid cells 2, gene containing a R47H point mutation, with two silent mutations.
The targeted Apoe gene encodes apolipoprotein E, which is important in lipoprotein metabolism and cardiovascular disease as well as Alzheimer’s disease, immunoregulation and cognition. The targeted Trem2 gene encodes a protein that is part of a receptor signaling complex with TYRO protein tyrosine kinase binding protein, and that activates macrophages and dendritic cells during immune responses. The TREM2 R47H mutation is a missense mutation in exon 2 that is one of the strongest genetic risk factors for late-onset Alzheimer’s disease.
Mice that are homozygous for the Apoe^{tm1.1(APOE*4)Adiuj} and Trem2^em1Adiuj alleles and heterozygous for the Plcg2^em2Adiuj allele are viable and fertile. Homozygous viability/fertility has not been tested for the Plcg2^em2Adiuj allele (June 2018).
As the mice are characterized, we will modify the strain description and add phenotype data.

Of note, in brains of mice homozygous for the Trem2^em1Adiuj allele (and not carrying any other mutant alleles), expression of both transcripts of Trem2 is decreased by about 50%. Mice expressing the Trem2 R47H mutation also express a novel splice variant with a deletion of 119bp at the 5’ end of exon 2, due to a cryptic splice acceptor site in exon 2 (see Stock No. 027918).

Development

This triple mutant line was generated by was generated by utilizing CRISPR/cas9 endonuclease mediated genome editing of the Plcg2 (phospholipase C, gamma 2) gene in
B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J (Stock No. 028709) mice.

For the Apoe^{tm1.1(APOE*4)Adiuj} allele (available as Stock No. 027894):
A targeting vector containing a 3' FRT flanked neo cassette was used to replace exons 2, 3 and most of exon 4 with 1.5 kb of human APOE gene sequence including exons 2, 3 and 4 (and some 3' UTR sequence). The human ApoE sequence also contains a 2 nucleotide A to T substitution in intron 3 for identification of the targeted allele by Southern analysis. The construct was electroporated into C57BL/6J derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission by crossing to C57BL/6J. Heterozygous animals were crossed subsequently to FLP recombinase expressing mice (see Stock No. 005703) to remove the FRT site flanked PGK-neo cassette. Mice that no longer contained the FRT flanked PGK-neo cassette were then backcrossed to C57BL/6J at least once to remove the FLP recombinase transgene.

For the Trem2^em1Adiuj allele (available as Stock No. 027918):
Plasmids encoding a single guide RNA designed to introduce a R47H point mutation, with two silent mutations, into the Trem2 gene and the cas9 nuclease were introduced into the cytoplasm of C57BL/6J-derived fertilized eggs with well recognized pronuclei. Correctly targeted embryos were transferred to pseudopregnant females. Correctly targeted pups were identified by sequencing and PCR and further bred to C57BL/6J mice (Stock No. 000664) to develop the colony.

For the Plcg2^em2Adiuj allele:
plasmids encoding a single guide RNA designed to introduce the M28L mutation into the Plcg2 gene and the cas9 nuclease were introduced into the cytoplasm of B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J (Stock No. 028709) derived fertilized eggs with well recognized pronuclei. Correctly targeted embryos were transferred to pseudopregnant females. Correctly targeted pups were identified by sequencing and PCR and further bred to B6(SJL)-Apoe^{tm1.1(APOE*4)Adpmc} Trem2^em1Adpmc/J (Stock No. 028709) to develop the colony.

Expression Data

Expressed Gene	APOE, apolipoprotein E, human
Site of Expression
Site of Expression

Control Suggestions

B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J mice (Stock No. 028709) may be an appropriate control.

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)	Trem2^em1Adiuj; endonuclease-mediated mutation 1, MODEL-AD Center
Gene Symbol and Name	Trem2, triggering receptor expressed on myeloid cells 2
Gene Synonym(s)	TREM-2; Trem2b; Trem2c; Trem2a; Trem2b; Trem2c; triggering receptor expressed on myeloid cells 2c; Trem2a; triggering receptor expressed on myeloid cells 2a; triggering receptor expressed on myeloid cells 2b; PLOSL2
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^{tm1.1(APOE*4)Adiuj}; targeted mutation 1.1, MODEL-AD Center
Gene Symbol and Name	Apoe, apolipoprotein E
Gene Synonym(s)	expressed sequence AI255918; APO-E; AD2; LPG; AI255918; LDLCQ5; APOEA; ApoE4
Expressed Gene	APOE, apolipoprotein E, human
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.

Plcg2^em3Adiuj

Allele Symbol: Plcg2^em3Adiuj

Allele Name	endonuclease-mediated mutation 3, MODEL-AD Center
Allele Type	Endonuclease-mediated (Humanized sequence)
Allele Synonym(s)	Plcg2^em3Adiuj; endonuclease-mediated mutation 3, MODEL-AD Center
Gene Symbol and Name	Plcg2, phospholipase C, gamma 2
Gene Synonym(s)	FCAS3; APLAID; MGC:38590; Plcg-2; Plcg-2; PLCgamma2; PLC-gamma-2; PLC-IV
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 Genotype

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

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

Mammalian Phenotype Terms by Genotype

References

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

Additional - Plcg2^em3Adiuj related

Additional - Trem2^em1Adiuj related

Technical Support

Contact Technical Support

Genotyping Protocols
- End Point Analysis:Trem2^em1Adiuj
- Standard PCR:Apoe^{tm1.1(APOE*4)Adiuj}
- End Point Analysis:Plcg2^em3Adiuj
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, mice homozygous for the Apoe^{tm1.1(APOE*4)Adiuj} and Trem2^em1Adiuj, and heterozygous for the Plcg2^em2Adiuj allele may be bred. Homozygous viability/fertility has not been tested for the Plcg2^em2Adiuj allele (June 2018). As the mice are characterized, we will modify the strain description if necessary and add data related to viability and fertility.
- Additional Breeding and Husbandry Support
Mating System
- Homozygous for Apoe^{tm1.1(APOE*4)Adiuj} Heterozygous for Plcg2^em3Adiuj Homozygous for Trem2^em1Adiujx Homozygous for Apoe^{tm1.1(APOE*4)Adiuj} Wildtype for Plcg2^em3Adiuj Homozygous for Trem2^em1Adiuj
  ^or
  Homozygous for Apoe^{tm1.1(APOE*4)Adiuj} Wildtype for Plcg2^em3Adiuj Homozygous for Trem2^em1Adiuj X Homozygous for Apoe^{tm1.1(APOE*4)Adiuj} Heterozygous for Plcg2^em3Adiuj Homozygous for Trem2^em1Adiuj
Citation
When using the Plcg2*M28L/APOE4/Trem2*R47H mouse strain in a publication, please cite the originating article(s) and include JAX stock #030674 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Homozygous for Apoe<tm1.1(APOE*4)Adiuj> and Trem2<em1Adiuj> Heterozygous or wildtype for Plcg2<em3Adiuj>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Apoe<tm1.1(APOE*4)Adiuj> Plcg2<em3Adiuj> Trem2<em1Adiu	$2595.00
Frozen Mouse Embryo	B6.Cg-Apoe<tm1.1(APOE*4)Adiuj> Plcg2<em3Adiuj> Trem2<em1Adiu	$2595.00
Frozen Mouse Embryo	B6.Cg-Apoe<tm1.1(APOE*4)Adiuj> Plcg2<em3Adiuj> Trem2<em1Adiu	$3373.50
Frozen Mouse Embryo	B6.Cg-Apoe<tm1.1(APOE*4)Adiuj> Plcg2<em3Adiuj> Trem2<em1Adiu	$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.

Terms Of Use

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

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As: Plcg2*M28L/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

Plcg2em3Adiuj

Allele Symbol: Plcg2em3Adiuj

Disease Terms

Research Areas By Genotype

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 - Plcg2em3Adiuj related

Additional - Trem2em1Adiuj related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Plcg2M28L/APOE4/Trem2R47H

Trem2^em1Adiuj

Allele Symbol: Trem2^em1Adiuj

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

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

Plcg2^em3Adiuj

Allele Symbol: Plcg2^em3Adiuj

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

Additional - Plcg2^em3Adiuj related

Additional - Trem2^em1Adiuj related