Overview

These TL-deficient mice harbor mutations in both alleles encoding the non-classical major histocompatibility complex (MHC) class I thymus leukemia (TL) antigen; a targeted "knockout" mutation of the H2-T3 gene (histocompatibility 2, T region locus 3) and also the nonfunctional allele of the H2-T18 gene (histocompatibility 2, T region locus 18) from the C57BL/6 genetic background. Because expression of TL antigen from either locus is absent from intestinal epithelial cells (IEC) and small/large intestine tissues, these TL-deficient mice may be useful in studying thymus leukemia (TL) antigen-deficiency on CD8αα intraepithelial lymphocytes, and the regulation of intraepithelial lymphocyte effector functions (for example, acceleration of chronic colitis and inflammatory bowel disease).

Donating Investigator

Dr. Luc Van Kaer, Vanderbilt University School of Medicine

Genetic overview

Genetic Background	Generation

H2-T3^tm1Luc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	H2-T3	histocompatibility 2, T region locus 3

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The mouse thymus leukemia (TL) antigen is a nonclassical MHC class I molecule encoded by a locus within the MHC complex harboring two genes; H2-T3 and H2-T18. TL binds with high affinity to the CD8αα molecule expressed on the vast majority of intraepithelial lymphocytes (IEL), and the interaction of CD8αα with TL is important for lymphocyte regulation in the intestine. The C57BL/6 genetic background normally has the functional H2-T3^d allele and a mutant H2-T18^b allele known to result in no expression on the surface of intestinal epithelial cells (IEC). Because these mutant mice harbor a targeted mutation of the H2-T3 gene that abolishes gene function, expression of TL protein (antibody staining) and RNA (RT-PCR) from either locus is absent in IEC and small/large intestine, respectively. These TL-deficient mice may be useful in studying thymus leukemia (TL) antigen-deficiency on CD8αα intraepithelial lymphocytes, and the regulation of intraepithelial lymphocyte effector functions (for example, acceleration of chronic colitis and inflammatory bowel disease).

Development

A targeting vector was designed to replace part of exon 3 of the targeted gene with a neomycin resistance cassette. The targeting construct was electroporated into C57BL/6-derived BL/6-III embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J females. Mutant mice were then bred together for many generations prior to sending to The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the mutant colony.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Olivares-Villagomez D; Mendez-Fernandez YV; Parekh VV; Lalani S; Vincent TL; Cheroutre H; Van Kaer L. 2008. Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease. Proc Natl Acad Sci U S A 105(46):17931-6PubMed: 19004778 MGI: J:142515

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Genetics

H2-T3^tm1Luc

Allele Symbol: H2-T3^tm1Luc

Allele Name	targeted mutation 1, Luc Van Kaer
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	TL^-
Gene Symbol and Name	H2-T3, histocompatibility 2, T region locus 3
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	17
Molecular Note	Depending on the background strain, thymic leukemia antigen (TL) can be encoded by one to three genes. This locus contains the sole gene encoding TL antigen in C57BL/6 mice. Exon 3 of the gene was disrupted by the insertion of a neomycin resistance cassette. Gene inactivation was confirmed in homozygote C57BL/6 mice by a lack of TL antigen detected by flow cytometry on intestinal epithelium.
Mutations Made By	Dr. Luc Van Kaer, Vanderbilt University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin
  - T cell deficiency
  - T cell specific surface marker
  - specific T cell deficiency
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: T cell specific surface marker
- Cancer Research
  - T cell deficiency
  - specific T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - specific T cell deficiency
  - MHC class I deficiency
  - T cell deficiency
  - Inflammatory bowel disease
- Autoimmunity
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Inflammation
  - Inflammatory bowel disease
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency
- Gastrointestinal Defects
  - colitis

Mammalian Phenotype Terms by Genotype

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

Genotype: H2-T18^b/H2-T18^b H2-T3^tm1Luc/H2-T3^tm1Luc
C57BL/6-H2-T3

immune system phenotype

abnormal intraepithelial T cell morphology
- IEL activation by low amounts of plate bound anti-CD3 is enhanced compared to controls
- enhanced proliferation of IELs can be suppressed to wild-type levels when cultured in the presence of tumor cells bearing TL antigen
- differences at higher doses of anti-CD3 are not significant

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- colonic alpha-beta IELs expressing CD8-alpha homodimers have almost a 2-fold higher homeostatic proliferation rate in vivo
- when epithelial cells are removed from IEL culture, there is no longer a difference in the proliferative responses of IEL to anti-CD3
- enriched small intestine alpha-beta IEL have enhanced proliferation compared to controls in response to low amounts of plate bound anti-CD3

abnormal CD8-positive, gamma-delta intraepithelial T cell morphology
- colonic gamma-delta IELs expressing CD8-alpha homodimers have almost a 3-fold higher homeostatic proliferation rate in vivo

increased interferon-gamma secretion
- intestinal intraepithelial lymphocytes have enhanced IFN-gamma secretion in response to anti-CD3 stimulation

hematopoietic system phenotype

abnormal CD8-positive, gamma-delta intraepithelial T cell morphology
- colonic gamma-delta IELs expressing CD8-alpha homodimers have almost a 3-fold higher homeostatic proliferation rate in vivo

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- when epithelial cells are removed from IEL culture, there is no longer a difference in the proliferative responses of IEL to anti-CD3
- colonic alpha-beta IELs expressing CD8-alpha homodimers have almost a 2-fold higher homeostatic proliferation rate in vivo
- enriched small intestine alpha-beta IEL have enhanced proliferation compared to controls in response to low amounts of plate bound anti-CD3

abnormal intraepithelial T cell morphology
- IEL activation by low amounts of plate bound anti-CD3 is enhanced compared to controls
- enhanced proliferation of IELs can be suppressed to wild-type levels when cultured in the presence of tumor cells bearing TL antigen
- differences at higher doses of anti-CD3 are not significant

References

Olivares-Villagomez D; Mendez-Fernandez YV; Parekh VV; Lalani S; Vincent TL; Cheroutre H; Van Kaer L. 2008. Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease. Proc Natl Acad Sci U S A 105(46):17931-6PubMed: 19004778 MGI: J:142515

Additional - H2-T3^tm1Luc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:H2-T3
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice may be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the C57BL/6-H2-T3^tm1Luc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008711 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 H2-T3<tm1Luc>

Related Products and Services

Frozen Mouse Embryo	C57BL/6-H2-T3<tm1Luc>/J	$2595.00
Frozen Mouse Embryo	C57BL/6-H2-T3<tm1Luc>/J	$2595.00
Frozen Mouse Embryo	C57BL/6-H2-T3<tm1Luc>/J	$3373.50
Frozen Mouse Embryo	C57BL/6-H2-T3<tm1Luc>/J	$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

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

H2-T3tm1Luc

Allele Symbol: H2-T3tm1Luc

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: H2-T18b/H2-T18b H2-T3tm1Luc/H2-T3tm1LucC57BL/6-H2-T3

immune system phenotype

hematopoietic system phenotype

References

Additional - H2-T3tm1Luc 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

H2-T3^tm1Luc

Allele Symbol: H2-T3^tm1Luc

Genotype: H2-T18^b/H2-T18^b H2-T3^tm1Luc/H2-T3^tm1Luc
C57BL/6-H2-T3

Additional - H2-T3^tm1Luc related