Overview

These LMP1^flSTOP mice allow inducible expression of EBV latent membrane protein 1 and have applications in studies of Epstein-Barr virus-induced immune surveillance and lymphomagenesis, and EBV-driven lymphoproliferative disorders.

Donating Investigator

Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine

Genetic overview

Genetic Background	Generation

Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence)	Gt(ROSA)26Sor	gene trap ROSA 26, Philippe Soriano

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Research Applications

Research Tools
Virology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These mice contain EBV latent membrane protein 1, Lmp1, coding sequence inserted into the Gt(ROSA)26Sor locus. LMP-1 (Epstein-Barr virus latent membrane protein 1) is a six-span transmembrane protein that is a functional, but dysregulated, mimic of CD40 signaling to B cells. Expression of the Lmp1 gene is blocked by a loxP-flanked STOP fragment placed between the Lmp1 sequence and the Gt(ROSA)26Sor promoter. When bred to mice that express Cre recombinase, the resulting offspring will have the STOP cassette deleted in the cre expressing tissue resulting in expression of Lmp1. Mice that are homozygous for the targeted mutation are viable and fertile.

For example, when bred to mice carrying Cd19^tm1(cre)Cgn (Stock No. 006785), Cre recombinase expression results in expression of LMP1 in B cells causing lymphoproliferation and lymphomagenesis.

Development

A targeting vector containing a splice acceptor, a floxed Neo^r-STOP cassette and the EBV latent membrane protein 1 (Lmp1) coding sequence (EBV B95-8 strain derived) was inserted into the Gt(ROSA)26Sor locus. The construct was electroporated into BALB/cJ derived Balb/C-I embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to BALB/c mice.
Upon arrival at The Jackson Laboratory, the mice were crossed to BALB/cJ (Stock No. 000651) at least once to establish the colony.

Expression Data

Expressed Gene	EBVS1, Epstein Barr virus integration site 1, human
Site of Expression

Control Suggestions

000651 BALB/cJ

Additional Information

Considerations for Choosing Controls

Genetics

Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}

Allele Symbol: Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}

Allele Name	targeted mutation 10, Klaus Rajewsky
Allele Type	Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence)
Allele Synonym(s)	LMP1^flSTOP
Gene Symbol and Name	Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano
Gene Synonym(s)
Expressed Gene	EBVS1, Epstein Barr virus integration site 1, human
Strain of Origin	BALB/cJ
Chromosome	6
Molecular Note	The construct containing (5' to 3') a splice acceptor, floxed neo stop cassette and EBV B95-8 strain Lmp1 coding sequence was inserted into the locus.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Genetics Research
  - Tissue/Cell Markers: Cre-lox System: ubiquitously expressed lox-STOP-lox-LacZ transgene
Virology Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}/Gt(ROSA)26Sor⁺ Cd19^tm1(cre)Cgn/Cd19⁺
involves: 129P2/OlaHsd * BALB/cJ

cellular phenotype

increased B cell proliferation
- and rarely into lungs and kidneys compared with control mice
- after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
- Normal - however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells

immune system phenotype

increased B cell proliferation
- after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
- Normal - however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
- and rarely into lungs and kidneys compared with control mice

increased CD4-positive, alpha beta T cell number
- at P8, but not P3, in the spleen
- of activated T cells in the bone marrow at 6 to 12 weeks

enlarged spleen
- 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)

decreased mature B cell number
- at 6 to 12 weeks in the bone marrow

increased CD8-positive, alpha-beta T cell number
- at P8, but not P3, in the spleen
- of activated T cells in the bone marrow at 6 to 12 weeks

abnormal B cell differentiation
- impaired in the bone marrow

abnormal CD8-positive, alpha-beta T cell physiology
- the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17

abnormal immune system physiology
- after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit splenomegaly and become terminally ill unlike control mice

increased pro-B cell number
- at 6 to 12 weeks in the bone marrow

decreased B cell number
- absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
- at 6 to 12 weeks in the spleen and bone marrow

decreased pre-B cell number
- at 6 to 12 weeks in the bone marrow

increased B cell number
- at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice

mortality/aging

increased sensitivity to induced morbidity/mortality
- 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)

growth/size/body region phenotype

enlarged spleen
- 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)

hematopoietic system phenotype

decreased B cell number
- absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
- at 6 to 12 weeks in the spleen and bone marrow

decreased pre-B cell number
- at 6 to 12 weeks in the bone marrow

increased B cell proliferation
- after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
- and rarely into lungs and kidneys compared with control mice
- Normal - however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells

abnormal CD8-positive, alpha-beta T cell physiology
- the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17

increased CD4-positive, alpha beta T cell number
- at P8, but not P3, in the spleen
- of activated T cells in the bone marrow at 6 to 12 weeks

increased pro-B cell number
- at 6 to 12 weeks in the bone marrow

abnormal B cell differentiation
- impaired in the bone marrow

enlarged spleen
- 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)

increased CD8-positive, alpha-beta T cell number
- at P8, but not P3, in the spleen
- of activated T cells in the bone marrow at 6 to 12 weeks

decreased mature B cell number
- at 6 to 12 weeks in the bone marrow

increased B cell number
- at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}/Gt(ROSA)26Sor⁺
involves: BALB/cJ

cellular phenotype

increased B cell proliferation
- B cells treated with TAT-cre proliferate in culture unlike wild-type cells

hematopoietic system phenotype

increased B cell proliferation
- B cells treated with TAT-cre proliferate in culture unlike wild-type cells

abnormal B cell morphology
- B cells treated with TAT-cre exhibit increased cell size compared with wild-type cells

immune system phenotype

abnormal B cell morphology
- B cells treated with TAT-cre exhibit increased cell size compared with wild-type cells

increased B cell proliferation
- B cells treated with TAT-cre proliferate in culture unlike wild-type cells

References

Additional References

Zhang B; Kracker S; Yasuda T; Casola S; Vanneman M; Homig-Holzel C; Wang Z; Derudder E; Li S; Chakraborty T; Cotter SE; Koyama S; Currie T; Freeman GJ; Kutok JL; Rodig SJ; Dranoff G; Rajewsky K. 2012. Immune Surveillance and Therapy of Lymphomas Driven by Epstein-Barr Virus Protein LMP1 in a Mouse Model. Cell 148(4):739-51PubMed: 22341446 MGI: J:181546

Additional - Gt(ROSA)26Sor^{tm10(Lmp1)Rsky} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Gt(ROSA)26Sor
- Separated PCR:Gt(ROSA)26Sor
- 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 BALB/c-Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019120 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
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Gt(ROSA)26Sor<tm10(Lmp1)Rsky>

Related Products and Services

Frozen Mouse Embryo	BALB/c-Gt(ROSA)26Sor<tm10(Lmp1)Rsky>/J	$2595.00
Frozen Mouse Embryo	BALB/c-Gt(ROSA)26Sor<tm10(Lmp1)Rsky>/J	$2595.00
Frozen Mouse Embryo	BALB/c-Gt(ROSA)26Sor<tm10(Lmp1)Rsky>/J	$3373.50
Frozen Mouse Embryo	BALB/c-Gt(ROSA)26Sor<tm10(Lmp1)Rsky>/J	$3373.50

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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

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Gt(ROSA)26Sortm10(Lmp1)Rsky

Allele Symbol: Gt(ROSA)26Sortm10(Lmp1)Rsky

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gt(ROSA)26Sortm10(Lmp1)Rsky/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+involves: 129P2/OlaHsd * BALB/cJ

cellular phenotype

immune system phenotype

mortality/aging

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Gt(ROSA)26Sortm10(Lmp1)Rsky/Gt(ROSA)26Sor+involves: BALB/cJ

cellular phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional References

Additional - Gt(ROSA)26Sortm10(Lmp1)Rsky 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

Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}

Allele Symbol: Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}

Genotype: Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}/Gt(ROSA)26Sor⁺ Cd19^tm1(cre)Cgn/Cd19⁺
involves: 129P2/OlaHsd * BALB/cJ

Genotype: Gt(ROSA)26Sor^{tm10(Lmp1)Rsky}/Gt(ROSA)26Sor⁺
involves: BALB/cJ

Additional - Gt(ROSA)26Sor^{tm10(Lmp1)Rsky} related