NOD.Cg-Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/DoiJ

Stock number: 004460
Product name: BDC2.5 TCR
Strain synonyms: NOD.BDC2.5
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

BDC2.5 transgenic mice express the rearranged T cell receptor genes Tcra and Tcrb from the diabetogenic H2-A^g7 restricted BDC2.5 Cd4⁺ T cell clone. When coupled with the homozygous Rag1^tm1Mom mutation (e.g. Stock No. 003729), mice develop diabetes extremely early at a mean age of 25 days.

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Detailed description

BDC2.5 transgenic mice express the rearranged T cell receptor (TCR) genes Tcra and Tcrb from the diabetogenic H2-A^g7 restricted BDC2.5 Cd4⁺ T cell clone. On the NOD background, mice carrying the transgene have a reduced incidence of diabetes (12% incidence by 20 weeks of age; Gonzalez, 1997) relative to NOD/ShiLtJ controls (Stock No. 001976).

When coupled with the homozygous Rag1^tm1Mom mutation (e.g. Stock No. 003729), mice develop diabetes extremely early at a mean age of 25 days (Gonzalez, 2001). Recombination of endogenous TCR and immunoglobulin (Ig) is prevented, so that mature T cells in the compound mutant mice express only the BDC2.5 TCR (Gonzalez, 2001; Mombaerts, 1992).

Development

This strain carries the rearranged T cell receptor genes Tcra and Tcrb from the diabetogenic H2-A^g7 restricted BDC2.5 Cd4⁺ T cell clone. The BDC2.5 Tcra and Tcrb sequences were co-injected into (B6xSJL)F2 eggs. To achieve the natural expression of Tcra, the rearranged VαJα sequence from BDC2.5 was cloned into the cosH-Yα9.1-36 cassette vector generated by Kouskoff (PMID: 7714342), which contains both the 5' upstream promoter and the 3' downstream enhancer regions of the Tcra gene. The BDC2.5 Tcrb VβDβJβ sequence, along with its 5' regulatory sequences and 3' enhancer region, was cloned into the construct generated by Signorelli (PMID: 1327799) upstream of the Cβ2 constant region. Transgenic mice were bred to NOD/ShiLt for over 10 generations. Through in situ hybridization, the integration site for these BDC2.5 TCR transgenes was localized to chromosome 13 near the D13mit125 marker.

Allele

Symbol: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi
Name: transgene insertion 1, Christophe Benoist
MGI accession ID: MGI:2181203
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: BDC2.5; BDC-2.5/N TCR Tg; Tg(TcraBDC2.5)2Doi; Tg(TcrbBDC2.5)2Doi
Marker symbol: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi
Marker name: transgene insertion 1, Christophe Benoist
Marker synonyms: Tg(TcraBDC2.5)1Doi; Tg(TcrbBDC2.5)1Doi; Tg(TcrbBDC2.5)2Doi
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F2
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: This transgene results from the coinjection of two constructs derived from diabetogenic T-cell clone BDC2.5. The Tcra construct contains a rearranged Tcra sequence (V alpha J alpha) that begins 20 bp 5' of the ATG site and ends 30 bp 3' of the splice donor sequence of J alpha 17. The 6.5 Tcrb construct contains rearranged Tcrb sequence (V beta D beta J beta) flanked by 2 kb of 5' regulatory sequences and 3.5 kb of 3' DNA containing the unrearranged J beta 1.3 to J beta 1.6 sequences, and precedes a 12 kb sequence containing the C beta 2 region.