NOD-Tg(TcraTcrb)2H6Lwn/J

Stock number: 017314
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These NOD background mice carry an autoreactive regulatory T cell receptor specific for insulin β chain peptide that renders them completely protected from diabetes development.

Detailed description

In addition to its biochemical functions, insulin can play an immunological role, acting as an autoantigen in human type I diabetes. In the NOD mouse model, many islet-reactive T cells invading the islet are insulin-specific. Studies suggest that insulin is also capable of generating a diabetes-protective immune response.

A regulatory/immunosuppressive T cell line (designated 2H6) was isolated from the pancreatic lymph nodes of a diabetic NOD mouse. These cells specifically recognize the insulin β chain peptide 12-25 or 9-23, secrete IFNG and TGFB, and have the ability to block both the adoptive transfer of diabetes in NOD-scid recipients and the spontaneous development of diabetes in NOD mice.

Based on this cell line, a transgenic strain that expresses the autoreactive 2H6 Vα6/Vβ14 regulatory T cell receptor was created on the NOD genetic background. Expression of the transgene blocks CD8+ T cell development. These mice are completely protected from diabetes development and upon binding express significant amounts of IFNG and TGFB. Cells from these mice can differentiate into potent regulatory cells that can protect NOD mice from the aggressive effects of spleen cells transferred from diabetic mice and diabetogenic cells from BDC2.5 transgenic mice.

No phenotypic differences between hemizygotes and homozygotes have been found.

This strain has been useful in studies of regulatory T cell (Treg) function and in the development of therapies for autoimmune disorders.

Development

The donating laboratory isolated and cloned a regulatory/immunosuppressive T cell line (designated 2H6) from the pancreatic lymph nodes of a diabetic NOD mouse that specifically recognizes the insulin B chain peptide 12-25 or 9-23.

2H6 regulatory TCRα (Vα6 (Vα6/Jα45/Cα)) and TCRβ (Vβ14 (Vβ14/Dβ1.1Jβ2.3Cβ2)) constructs were directly coinjected into fertilized NOD oocytes to create a transgenic line. This strain was maintained on an NOD genetic background by the donating laboratory.

Allele

Symbol: Tg(TcraTcrb)2H6Lwn
Name: transgene insertion 2H6, Li Wen
MGI accession ID: MGI:5141276
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: 2H6 TCR transgenic
Marker symbol: Tg(TcraTcrb)2H6Lwn
Marker name: transgene insertion 2H6, Li Wen
Chromosome: UN
Strain of origin: NOD
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: The transgene contains the cloned regulatory/immunosuppressive T cell line (designated 2H6) from the pancreatic lymph nodes of a diabetic NOD mouse that specifically recognizes the insulin B chain peptide 12-25 or 9-23 (2H6 regulatory TCRalpha (Valpha6 (Valpha6/Jalpha45/Calpha)) and TCRbeta (Vbeta14 (Vbeta14/Dbeta1.1Jbeta2.3Cbeta2))).