C57BL/6-H2-T3^tm1Luc/J

Stock number: 008711
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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).

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.

Allele

Symbol: H2-T3^tm1Luc
Name: targeted mutation 1, Luc Van Kaer
MGI accession ID: MGI:3822740
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: H2-T3
Marker name: histocompatibility 2, T region locus 3
Chromosome: 17
Strain of origin: C57BL/6
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.