B10.Cg-H2^d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ

Stock number: 005308
Product name: clone 4 TCR
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These transgenic mice express a T-cell receptor specific for an epitope of hemagglutinin that is restricted by MHC class I H2-K^d.

Detailed description

Transgenic mice are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities.The TCR expressed from this transgene is specific for influenza virus A/PR/8 hemagglutinin (HA) in the context of the MHC class I molecule H2-K^d. Both thymic and peripheral T-cell populations are skewed toward CD8+ cells. The majority of thymocytes and virtually all CD8+ T cells in lymph nodes express the transgenic TCR beta chain. About 40% of peripheral blood CD8+ T cells react with the HA peptide presented by H2-K^d. When mated with Tg(Ins2-HA)165Bri, double transgenic neonates have similar levels of V-beta 8 and total number of thymocytes as Tg(TcraCl4,TcrbCl4) mice however the double transgenics become spontaneously diabetic after birth and die within 10 days.

This transgenic model is useful in the study of T-cell activation, cross presentation of antigens, process of thymic selection, peripheral tolerance and the immune response to influenza.

Development

The Tcra and Tcrb transgenes encode a Tcr cDNA from Clone 4 derived from a B10.D2-Hc¹ H2^d H2-T18^c/nSn mouse previously immunized with Influenza virus A/PR/8. The clone 4 transgenic constructs were co-injected and co-inserted in (C57BL/6 x BALB/c)F1 oocytes. Transgene positive mice were backcrossed to B10.D2-Hc¹ H2^d H2-T18^c for 20 generations. In 2005, The Jackson Laboratory received B10.Cg-H2^d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ (Clone4 TCR) at generation N20 and backcrossed it to B10.D2-Hc¹ H2^d H2-T18^c/nSnJ (Stock No. 000463) one generation prior to maintaining by brother-sister matings.

Allele

Symbol: Tg(TcraCl4,TcrbCl4)1Shrm
Name: transgene insertion 1, Linda Sherman
MGI accession ID: MGI:3586582
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcraCl4,TcrbCl4)1Shrm
Marker name: transgene insertion 1, Linda Sherman
Chromosome: UN
Strain of origin: (C57BL/6 x BALB/c)F1
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Site of expression: T-cells.
Molecular note: Tcra and Tcrb cDNAs were isolated from Clone-4, a CTL line derived from a B10.D2-Hc¹ H2^d H2-t18^c/nSnJ mouse immunized with influenza virus A/PR/8. A Tcra cDNA fragment representing the V-J exon, containing Valpha10, was cloned into a Tcra shuttle vector that includes a mouse Tcra-V promoter, the immunoglobulin heavy-chain enhancer E_H, and the Tcra-C genes with some flanking DNA. Likewise, a Tcrb cDNA fragment representing the VDJ exon, containing Vbeta8.2, was cloned into a Tcrb shuttle vector including a mouse Tcrb-V promoter, E_H, and the Tcrb-C genes with some flanking DNA. The plasmid constructs were coinjected. This transgenic TCR specifically recognizes influenza virus A/PR/8 hemagglutinin restricted by MHC class I H2k^d.

Allele

Symbol: Hc¹
Name: sufficient
MGI accession ID: MGI:3044820
Generation method: Not Applicable
Marker symbol: Hc
Marker name: hemolytic complement
Chromosome: 2
Strain of origin: multiple strains
Molecular note: This allele does not contain the 2 base "TA" deletion found in the Hc⁰ allele and is found in the following mouse strains BALB/cJ, C57BL/6J, DBA/1J, and B10.D2/nSnJ. This is equivalent to the wild-type allele.
General note:

Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The C3H/HeJ allele does not have the 2 bp deletion and is associated with resistance to allergen-induced bronchial hyperresponsiveness. (J:108211)

Allele

Symbol: H2^d
Name: d variant
MGI accession ID: MGI:3579320
Generation method: Spontaneous
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Chromosome: 17
Strain of origin: various
General note: The d variant has been observed in the following strains: DBA/2, DBA/2J BALB/c, BALB/cByJ, BALB/cJ, C57BLKS, NZB.

Allele

MGI accession ID: MGI:95950
Marker symbol: H2-T18
Marker name: histocompatibility 2, T region locus 18
Chromosome: 17