NOD.Cg-Tg(HLA-A2/H2-K)1Scr/ShrmJ

Stock number: 005853
Product name: NOD.HLA-A2/Kb
Strain synonyms: NOD CyA2/Kb, NOD.A2/Kb
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These NOD.HLA-A2/Kb mice express a transgene containing a human-mouse chimeric major histocompatibility class I protein composed of the human HLA-A2.1 joined to the mouse H2-K^b and exhibit HLA-A2.1-restricted CD8 T-cell responses to appropriate antigens.

Detailed description

Transgenic mice are viable, fertile, normal in size and do not display any behavioral abnormalities. FACs analysis indicates expression of HLA-A201 on peripheral blood lymphocytes. The level of expression of this chimeric MHC I molecule in transgenic mice is similar to the observed expression in human PBL's. Diabetes incidence of mice carrying this transgene (88%) is similar to NOD (79%) at 25 weeks of age. Splenocytes from transgenic mice immunized with GAD65 peptides together with MHC class II helper peptide were re-stimulated with peptide pulsed irradiated syngeneic APC?s in-vitro 10 days post immunization Transgenic mice immunized with three different GAD65 peptides (position: 144-149, sequence: LLQEYNWEL; position: 114-122, sequence: VMNILLQYV; and position 573-581, sequence: FLIEEIERL) gave vigorous CTL responses when tested by standard chromium release assays. FACs analysis indicates presence of CFSE expression on CD8⁺ T-cells in transgenic mice given CFSE-labeled CD8⁺ T cells in the pancrease, but not in the peripheral or pancreatic lymph nodes 4 days post injection. CFSE-positive CD8⁺ T-cells were absent in the pancreas, peripheral and pancreatic lymph nodes of wildtype mice. This model provides a tool to identify MHC class I epitopes recognized by CD8⁺ T cells in type 1 diabetes patients, in addition to testing new therapies focusing on restoring immune tolerance.

Development

NOD mice carrying a CD8⁺ T-cell transgene (HLA-A2/H2-K)1Scr express the alpha 1 and alpha2 domain of the human class 1 molecule, HLA-A201, fused to the alpha 3, transmembrane and cytoplasmic domains of the mouse H-2k^b molecule. This transgene was injected into C57BL/6J oocytes. Resulting progeny were backcrossed to NOD for 14 generations. In 2006, The Jackson Laboratory received NOD.Cg-Tg(HLA-A2/H2-K)1Scr/ShrmJ at generation N14.

Allele

Symbol: Tg(HLA-A2/H2-K)1Scr
Name: transgene insertion 1, The Scripps Research Institute
MGI accession ID: MGI:3050815
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(HLA-A2/H2-K)1Scr
Marker name: transgene insertion 1, The Scripps Research Institute
Chromosome: UN
Strain of origin: C57BL/6J
Expressed genes: HLA-A2.1,major histocompatibility complex, class I, subtype A2.1,human; H2-K,histocompatibility 2, K region,mouse, laboratory
Molecular note: The transgene expresses a human-mouse chimeric major histocompatibility class I protein composed of the leader sequence and the alpha1 and alpha2 domains of HLA-A2.1 joined to the alpha3, cytoplasmic and transmembrane domains of H2-K^b. Mice expressing this transgene exhibit HLA-A2.1-restricted CD8 T-cell responses to appropriate antigens.