NOD.Cg-H2-K1^d-em1Dvs H2-Ab1^g7-em1Dvs H2-D1^b-em5Dvs Tg(HLA-A/H2-D/B2M)1Dvs Tg(HLA-DQA1,HLA-DQB1)1Dv Tg(CD2-Tcra20D11,Cd4-Tcrb20D11)1Dvs/DvsJ

Stock number: 036578
Product name: NOD-cMHCI/II^-/-.DQ8-A2-20D11 , cMHCKO.DQ8-A2-20D11.1 , DQ8-A2-20D11
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

NOD-cMHCI/II^-/-.DQ8-A2-20D11 (DQ8-A2-20D11) mice express both HLA-DQ8 and HLA-A2 while lacking classical murine MHC molecules. This allows the selection of both CD4⁺ and CD8⁺ T cells that are human HLA-DQ8 or HLA-A2 restricted. The mice also express DQ8-restricted human TCR 20D11 recognizing insulin B_9-23 (derived from T1D donor nPOD6323). These mice do not develop Type I diabetes (T1D) or develop myocarditis. This strain is one of a series of mouse models expressing various combinations of HLA I and II alleles plus or minus transgenes encoding disease-relevant human TCRs (hTCRs) isolated from type I diabetes (T1D) patients (Racine, 2023 – PMID: 37877672).

Detailed description

Development of Type 1 diabetes (T1D) is associated with specific major histocompatibility class I and class II variants in both humans and mouse. NOD-cMHCI/II^-/-.DQ8-A2-20D11 (DQ8-A2-20D11) mice are deficient in classical MHC class I (cMHCI) expression (H2-K1^d-em1Dvs, H2-D1^b-em5Dvs), lack classical MHC class II (cMHCII) molecules (H2-Ab1^g7-em1Dvs), and express transgenes encoding (1) human HLA-DQ8 (HLA-DQA*0301, DQB*0302), (2)  human β 2-microglubulin (B2M) covalently linked to the MHC class I, -alpha1 and alpha2 antigen binding domains of the human HLA-A2.1 (HLA-A*02:01) gene and the alpha3, cytoplasmic and transmembrane domains of murine H2-D1^b (Tg(HLA-A/H2-D/B2M)1Dvs), and (3) a DQ8-restricted human TCR 20D11 recognizing insulin B_9-23.

Despite the lack of overt T1D, DQ8-A2-20D11 mice have increased insulitis compared with either A2 (Stock No. 031433) or DQ8-A2 (Stock No. 039054) mice, and they lack the myocarditis found in either DQ8 (Stock No. 039053) or DQ8-A2 (stock No. 039054) mice. Insulitis is, however, reduced in comparison with surviving NOD controls.

Development

DQ8-20D11 (NOD.Cg-H2-K1^d-em1Dvs H2-Ab1^g7-em1Dvs H2-D1^b-em5Dvs Tg(HLA-DQA1,HLA-DQB1)1Dv Tg(CD2-Tcra20D11,Cd4-Tcrb20D11)1Dvs/Dvs; Stock No. 035480) and DQ8-A2 (NOD.Cg-H2-K1^d-em1Dvs H2-Ab1^g7-em1Dvs H2-D1^b-em5Dvs Tg(HLA-A/H2-D/B2M)1Dvs Tg(HLA-DQA1,HLA-DQB1)1Dv/DvsJ; Stock No. 039054) mice were intercrossed to generate this NOD-cMHCI/II^−/−.DQ8-A2-20D11 strain (DQ8-A2-20D11; Stock No. 036578). The integration site and the copy number of the HLA and TCR transgenes are unknown (December, 2023).