B10.Cg-Tg(CD2-TcraTrav16,H2-K1-TcrbTrbv5)R161HRrc H2^r H2-T18^b/RrcJ

Stock number: 039939
Product name: R161H
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

The Jackson Laboratory is unable to ship this strain as live mice due to the hemizygous eye phenotype [bilateral peripheral lymphohistiocytic keratitis, scleritis (lymphohistiocytic infiltrate)] that develops as early as ~4 weeks of age and is fully penetrant by ~8 weeks of age. Please contact Customer Service for information on the availability of frozen materials.

The R161H mice have transgene expressing multiple copies of TCR α and β chains specific to the retinal antigen IRBP (Rbp3) cloned from a highly uveitogenic T cell line. Hemizygous mice show 100% penetrance of spontaneous uveitis and the highest disease severity with onset around weaning age that reaches 100% incidence by 2 months. These mice are useful for studying the development of autoimmune uveitis and as donors of naive autoantigen-specific T cells for mechanistic studies in autoimmune disease research.

Detailed description

In R161H mice, the transgenes express TCR α and β chains cloned from a highly uveitogenic T cell line, specific to the interphotoreceptor retinoid-binding protein (IRBP) 161-180 sequences. The IRBP 161-180 sequence encodes a major pathogenic epitope for B10.RIII (Stock No. 000457) mice that are highly susceptible to experimental autoimmune uveitis (EAU) induced by immunization. The R161H line is one of the 3 founder lines and has the highest expression of the transgene. The donating laboratory reports that hemizygous mice are viable and fertile, with 100% penetrance of spontaneous inflammatory-like pathologies in the middle and outer layers of eyes with onset around weaning age that reaches 100% incidence by 2 months. Pathology performed by The Jackson Laboratory on 8 week old hemizygotes (n=4) and 12 week old hemizygotes (n=4) found that all mice examined had bilateral peripheral lymphohistiocytic keratitis and scleritis (lymphohistiocytic infiltrate).

The donating laboratory reported that mice appear healthy despite eye disease and live long enough to maintain the colony (6 months to 1 year). Some Tg mice develop thymoma or lymphoma incidence later in their life after 4 months. Their study demonstrated that microbiota affects disease, and depleting microbiota (by broad-spectrum antibiotics or by making "germ-free") significantly attenuated uveitis.

Of note, in addition to these mice, the donating investigator provided The Jackson Laboratory Repository with R161M (Stock No. 039940).

Development

T-cell line was originally derived from highly EAU-susceptible B10.RIII (Stock No. 000457) mice that had been immunized with the major pathogenic peptide of IRBP, residues 161-180 (SGIPYIISYLHPGNTILHVD), by repeated stimulations with the IRBP161-180 peptide followed by expansion in IL-2-containing medium. A transgene containing the cloned Tcra and Tcrb cDNA sequences identified as Trav16 and Trbv5 were placed under the control of the human CD2 promoter and H-2K promoter, respectively. The resulting transgene constructs containing Trav16 (11.3 kb) and Trbv5 (6.1 kb) were microinjected together into B10.RIII (Stock No. 000457) embryos. One founder line, R161H, carrying both TCR genes was bred to B10.RIII wild type (WT) mice and expanded into transgenic lines by the donating investigator, who reported that 5 copies of Trav16 and 8 copies of Trbv5 tandem repeats of the transgene are inserted into chromosome 9. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize B10.RIII oocytes (Stock No. 000457).

Allele

Symbol: H2^r
Name: r haplotype
MGI accession ID: MGI:5780884
Generation method: Not Applicable
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Marker synonyms: H-2; MHC-II
Chromosome: 17
Strain of origin: RIII

Allele

Symbol: H2-T18^b
Name: b variant
MGI accession ID: MGI:4820508
Generation method: Not Applicable
Attributes: Not Applicable
Synonyms: TL^-; Tla^b
Marker symbol: H2-T18
Marker name: histocompatibility 2, T region locus 18
Marker synonyms: H-2T18; TL Ag; Tla
Chromosome: 17
Strain of origin: Not Applicable
Molecular note: The allele H2-T18^b determines absence of the antigen (TL^-) and occurs in strains C57BL/6, AKR, C3H/An, and many others.

Allele

Symbol: Tg(CD2-TcraTrav16,H2-K1-TcrbTrbv5)R161HRrc
Name: transgene insertion R161H, Rachel R Caspi
MGI accession ID: MGI:7790611
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: R161H
Marker symbol: Tg(CD2-TcraTrav16,H2-K1-TcrbTrbv5)R161HRrc
Marker name: transgene insertion R161H, Rachel R Caspi
Chromosome: 9
Strain of origin: B10.RIII-H2^r H2-T18^b/(71NS)SnJ
Molecular note: The transgene contains, TCR α and β chains were cloned from a highly uveitogenic T cell line, specific to the IRBP161–180 sequence, which encodes a major pathogenic epitope for B10.RIII mice, a strain highly susceptible to experimental autoimmune uveitis (EAU). The TCR a and b sequences were placed under control of the promoter and locus control region of the human CD2 gene, and the mouse H-2K promoter, respectively. This is high expressing line R161H having 5 TCR a and 8 TCR b tandem copies of the transgene inserted into the chromosome 9.