NOD.FVB-Tg(TcrbBDC12-4.1)82Gse/GseJ

Stock number: 006304
Product name: NOD.Tcrb BDC12-4.1
Strain synonyms: NOD.beta, BDC12-4.1 TCR beta82
Research areas: Diabetes and Obesity Research, Research Tools

Description

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

Detailed description

This transgenic strain carries a rearranged Tcr beta 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. 006303 - NOD.FVB-Tg(TcraBDC12-4.1)10Jos/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 observd 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. Further, approximately 50% of the TCR 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 beta transgenic strain when combined with the Tcr alpha strain (Stock No. 006303) 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 beta chain from the BDC12-4.1 was sub-cloned into a TCR cassette and microinjected into FVB embryos. Progeny from Founder line 82 progeny were backcrossed to NOD for 7 generations. In 2006, The Jackson Laboratory received hemizygous mice at generation N7 and backcrossed them three times to NOD/LtJ prior to sibling mating.

Allele

Symbol: Tg(TcrbBDC12-4.1)82Gse
Name: transgene insertion 82, George Eisenbarth
MGI accession ID: MGI:3687034
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcrbBDC12-4.1)82Gse
Marker name: transgene insertion 82, George Eisenbarth
Chromosome: UN
Strain of origin: FVB
Expressed genes: Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: The TCR beta (TRBV1*03/TRBJ2-7*01) chain from the BDC12-4.1 clone was subcloned into a TCR cassette.