NOD.FVB-Tg(TcraBDC12-4.1)10Jos/GseJ

Stock number: 006303
Product name: NOD.Tcra BDC12-4.1
Strain synonyms: NOD.alpha10, alpha10, BDC12-4.1 TCR alpha10
Research areas: Diabetes and Obesity Research, Research Tools

Description

These transgenic mice carry a rearranged Tcr alpha gene from the pathogenic anti-insulin CD4⁺ T-cell clone BDC12-4.1.

Detailed description

This transgenic strain carries a rearranged Tcr alpha gene from the pathogenic anti-insulin CD4⁺ T-cell clone BDC12-4.1. Transgenic mice are viable and fertile. When hemizygotes are crossed with Stock No. 006304 NOD.FVB-Tg(TcrbBDC12-4.1)82Gse/GseJ, expression of the BDC12-4.1 T-cell receptor is confirmed by FACS analysis of PBMCs from the double transgenic mice. Double transgenic mice develop insulitis, but spontaneous diabetes does not develop, even in older animals (60 weeks of age), nor can insulin autoantibodies be detected in any age group. Splenocytes from double transgenic mice stimulated with B9-23 peptide produce IFN-gamma, whereas no response is observed in controls. When the congenic NOD double transgenic is combined with a homozygous Rag1^tm1Mom mutation (such as in Stock No. 003729), recombination of the endogenous TCR and immunoglobulin genes is prevented. As a result, mature T cells in these mice express only the BDC12-4.1 TCR. In addition, approximately 50% of the double transgenic, Rag1^tm1Mom homozygote mice develop diabetes by 30 weeks of age. Histopathology indicates severe insulitis and/or destruction of all insulin-producing cells (Jasinski et al 2006). This Tcr alpha transgenic strain when combined with the Tcr beta strain (Stock No. 006304) is useful for further studying the pathogenesis of insulin autoimmunity and diabetes.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

BDC12-4.1 is a pathogenic CD4⁺ T cell clone derived from NOD pancreatic islets. The TCR specifically recognizes a mouse insulin B chain peptide (amino acids 9-23). The TCR alpha chain from the BDC12-4.1 was subcloned into a TCR cassette and microinjected into FVB embryos. Progeny from Founder Line 10 were backcrossed to NOD for 9 generations. In 2006, The Jackson Laboratory received hemizygous mice at generation N9 and backcrossed them once to NOD/LtJ prior to sibling mating.

Allele

Symbol: Tg(TcraBDC12-4.1)10Jos
Name: transgene insertion 10, Joslin Diabetes Center
MGI accession ID: MGI:3687036
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcraBDC12-4.1)10Jos
Marker name: transgene insertion 10, Joslin Diabetes Center
Chromosome: UN
Strain of origin: FVB
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory
Molecular note: The TCR alpha (TRAV5D-4*04/TRAJ53*01) chain from the BDC12-4.1 clone was subcloned into a TCR cassette.