C57BL/6-Tg(Tcra2D2,Tcrb2D2)1Kuch/J

Stock number: 006912
Product name: TCR^MOG
Strain synonyms: 2D2 TCR
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools, Sensorineural Research

Description

These 2D2 TCR (TCR^MOG) transgenic mice express a myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor. Hemizygotes develop spontaneous diseases similar in incidence and manifestation to those developed by multiple sclerosis patients. These mice may be useful for studying the myelin oligodendrocyte glycoprotein specific, self-reactive T cell repertoire, as well as to study optic neuritis and its relationship to the development of autoimmunity in the CNS.

Detailed description

2D2 TCR (TCR^MOG) transgenic mice express a myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor (TCR). Transgenic T cells are not deleted or tolerized, and are functionally competent. The majority of thymocytes in 2D2 TCR mice express high and intermediate levels of the receptor, indicating efficient positive selection of transgenic T cells. The majority of CD4⁺ splenocytes express the transgenic TCR (as defined by Valpha3.2 and Vbeta11 expression).

Cultured splenocytes are responsive to full-length MOG and to MOG 35-55 peptide, but not to ovalbumin (OVA) control peptides. Between 2.5 and 5 months of age, 4% of hemizygous 2D2 TCR mice are reported to develop spontaneous experimental autoimmune encephalomyelitis (EAE). Within the first year, 40% of 2D2 TCR mice develop spontaneous, isolated optic neuritis with neither clinical or histological evidence of EAE.

Standard EAE induction protocols produce typical EAE in 2D2 TCR mice, but injection of suboptimal doses of MOG is sufficient to trigger the optic neuritis without stimulating widespread EAE in the central nervous system (CNS). Because the spontaneous diseases observed in 2D2 TCR mice are similar in their incidence and manifestations to those developed by multiple sclerosis (MS) patients, these mice may be useful in immunological studies to investigate the role and nature of the MOG-specific, self-reactive T cell repertoire, as well as to study optic neuritis and its relationship to the development of autoimmunity in the CNS.

Development

A myelin oligodendrocyte glycoprotein (MOG) peptide (amino acids 35-55; MEVGWYRSPFSRVVHLYRNGK) was injected into C57BL/6 mice. T lymphocytes from lymph nodes of these immunized mice were isolated and cells expressing the T cell receptor (TCR) combination (Valpha3.2 and Vbeta11) were selected (clone 2D2). The Valpha3.2-Jalpha18 and Vbeta11-DJbeta1.1 sequences of 2D2 TCR were cloned into TCR expression cassettes and the resulting constructs were injected into the pronuclei of fertilized C57BL/6 oocytes. Founder mice were bred with C57BL/6J mice. These 2D2 TCR transgenic mice were bred with wildtype C57BL/6 for many generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Tg(Tcra2D2,Tcrb2D2)1Kuch
Name: transgene insertion 1, Vijay Kuchroo
MGI accession ID: MGI:3700794
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Tcra2D2,Tcrb2D2)1Kuch
Marker name: transgene insertion 1, Vijay Kuchroo
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: Tcrb,T cell receptor beta chain,mouse, laboratory; Tcra,T cell receptor alpha chain,mouse, laboratory
Molecular note: The Valpha3.2Jalpha18 region of Tcra from the 2D2 T cell clone as well as the Vbeta11DJbeta1,1 region of Tcrb from the same 2D2 clone were inserted into TCR expression cassettes. The linearized plasmids were injected into the pronuclei of fertilized C57BL/6 oocytes. The 2D2 clone was purified from C57BL/6 mice immunized with a peptide from myelin oligodendrocyte glycoprotein (MOG). The amino acid sequence of the CDR3 region from TCR alpha is VYF CALRSY NFG and that from TCR beta is CASS LDCG ANP.