B6.NOD-(D17Mit21-D17Mit10) Tg(TCRbAI4)1Dvs/DvsJ

Stock number: 004555
Product name: B6.H2^g7.AI4Β
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These B6.H2^g7.A14Β mice express a transgene containing a rearranged Tcrb derived from the pancreatic beta cell-reactive CD8 T lymphocyte clone AI4, and they exhibit reduced numbers of transgenic thymocytes and splenocytes compared to mice with the same transgene on a NOD background.

Detailed description

This strain when crossed with stock #004554 generates a C57BL/6J congenic that is transgenic for a diabetogenic TCR in the presence of the NOD-derived H2^g7. It is valuable in the assessment of non-MHC contributions to diabetogenesis from the C57BL/6J versus NOD inbred backgrounds. Compared with the TCR transgenic on the NOD background, this C57BL/6J congenic has a 31- and 4-fold reduction in the numbers of double positive and single positive transgenic thymocytes, respectively. The number of total splenocytes expressing this transgenic TCR is 1.7 fold lower than on the NOD background. However, while thymic negative selection is more efficient, the transgenic T cells that survive selection efficiently mediate diabetogenesis; all females were found to develop diabetes by 6 weeks of age, significantly faster than NOD mice with this transgenic TCR. The TCR transgenic T cells of C57BL/6J H2^g7 congenic TCR alpha and beta double transgenic mice have a greater rate of thymic emigration, a greater proliferative response to antigen presentation, display more potent killing of pancreatic islet cells in cytotoxicity assays, and have a higher cell surface expression level of transgenic TCR, specifically the TCR alpha chain, than found on the NOD background.

Development

The H2^g7 bearing interval from D17Mit21 to D17Mit10 was backcrossed from NOD/Ug onto C57BL/6 and fixed homozygous for the congenic interval at backcross generation N8 (see stock #003300 for details). The Tg(TCRbAI4)1Dvs transgene was generated by microinjection into NOD/ShiLt zygotes and was maintained on that background prior to being backcrossed onto the congenic B6.NOD-(D17Mit21-D17Mit10)/LtJ. At the N7 backcross generation this congenic was assessed and found to be homozygous for markers of all known C57BL/6J-derived insulin dependent diabetes (Idd) loci (Choisy-Rossi et al., 2004).

Allele

Symbol: Tg(TcrbAI4)1Dvs
Name: transgene insertion 1, David V Serreze
MGI accession ID: MGI:3057181
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcrbAI4)1Dvs
Marker name: transgene insertion 1, David V Serreze
Chromosome: UN
Strain of origin: NOD/ShiLt
Expressed genes: Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: The rearranged Tcrb transgene expressed in these mice is derived from the pancreatic beta cell-reactive CD8 T lymphocyte clone AI4. The transgenic construct contains a Tcrb-V2/Tcrb-D/Tcrb-J cDNA segment.
General note: In conjunction with Rag1^tm1Mom

transgenic mice carrying both the alpha and beta AI4 TCR transgenes exhibit an accelerated development of insulin-dependent diabetes mellitus (IDDM).

homozygous mice are viable and fertile

Allele

Symbol: H2^g7
Name: g7 variant
MGI accession ID: MGI:3579321
Generation method: Not Applicable
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Chromosome: 17
Strain of origin: Not Applicable
General note: The g7 variant has been observed in the following strains: DBR7, NON.NOD-H2^g7

Allele

MGI accession ID: MGI:90809
Marker symbol: D17Mit21
Marker name: DNA segment, Chr 17, Massachusetts Institute of Technology 21
Chromosome: 17

Allele

MGI accession ID: MGI:90738
Marker symbol: D17Mit10
Marker name: DNA segment, Chr 17, Massachusetts Institute of Technology 10
Chromosome: 17