NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ

Stock number: 005868
Product name: NOD.Tcr NY8.3
Strain synonyms: NOD-TCRalphabeta-TG, 8.3-TCR-alpha/beta transgenic NOD, NY8.3-NOD, NOD.8.3, 8.3-NOD
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ, commonly called 8.3-NOD or NY8.3, express rearranged Tcra and Tcrb transgenes derived from the pancreatic beta cell-cytotoxic CD8⁺ T cell clone NY8.3. Transgenic animals bearing both TCR transgenes offer a source of CTL precursors useful in examining the diversity of beta cell peptides recognized by the autoreactive CD8⁺ T lymphocytes contributing to the earliest phase of diabetes mellitus type 1 (IDDM) development.

Detailed description

NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ, commonly called 8.3-NOD or NY8.3, express rearranged Tcra and Tcrb transgenes derived from the pancreatic beta cell-cytotoxic CD8⁺ T cell clone NY8.3. CD4^-CD8⁺ thymocytes and lymph derived T cells are skewed toward VB8.1/2⁺ expression when compared to wild type controls. Although, transgenic mice exhibit dramatically accelerated diabetes, the cumulative diabetes incidence and kinetics of disease are remarkably similar to their wild type cohorts. Insulitis scores of 3 week old transgene⁺ mice was significantly lower, while insulitis scores of 6 week olds were significantly more severe than in wild types controls, Verdaguer, 1997.

Transgenic animals bearing both TCR transgenes offer a source of CTL precursors useful in examining the diversity of beta cell peptides recognized by the autoreactive CD8⁺ T lymphocytes contributing to the earliest phase of IDDM development.

The transcriptional coregulator OCA-B (Pou2af1) promotes expression of T cell target genes in cases of repeated antigen exposure, a necessary feature of autoimmunity. Knock-outs of Pou2af1 have been found to protect both NOD/ShiLtJ (Stock No. 001976) inbred mice and autoantigen-specific NY8.3 mice from spontaneous development of autoimmune diabetes. Protection is associated with large reductions in islet CD8+ T cell receptor specificities associated with diabetes pathogenesis. CD4+ clones associated with diabetes are present but associated with anergic phenotypes. (Kim, 2021).

Before 2020, FACS analysis (utilizing Vβ8.1,2,3 FITC antibody costaining with CD8a PE) was used to identify mice carrying this transgene. As of January 2020, The Jackson Laboratory is using genotyping to identify transgenic mice.

The accelerated diabetes development in NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ hemizygous breeding stock is not significantly retarded by Complete Freund's Adjuvant (CFA). If maintained in lower barrier mouse rooms, NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ mice will likely become diabetic at or before 8 weeks of age.

Development

(SJLXC57BL/6J)F2 transgenic mice were backcrossed to NOD. In 2005, the Type 1 Diabetes Resource received congenic NOD hemizygous transgenic mice backcrossed at least 14 generations to NOD.

Allele

Symbol: Tg(TcraTcrbNY8.3)1Pesa
Name: transgene insertion 1, Pere Santamaria
MGI accession ID: MGI:3584121
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcraTcrbNY8.3)1Pesa
Marker name: transgene insertion 1, Pere Santamaria
Chromosome: UN
Strain of origin: (SJL x C57BL/6)F2
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: Functional VDJbeta and VJalpha rearrangements were isolated from the beta cell cytotoxic CD8(+) T cell clone NY8.3. Upstream regulatory sequence together with either TCR-beta enhancers or TCR-alpha enhancers, as appropriate, were associated with VDJbeta or VJalpha.