Development of Type 1 diabetes (T1D) is associated with specific major histocompatibility Class I and Class II variants in both humans and mouse. In the mouse, the presence of the H2-Ag7 class II variant (homolog of DQ8 in humans) is a primary contributor to development of T1D. Susceptibility to T1D is also influenced by the expression of several class I variants in humans including HLA-A2 (Tg(HLA-A/H2-D/B2M)1Dvs) and HLA-B39 (Tg(HLA-B39/H2-D/B2m)2Dvs). Elimination of mouse MHC Class I expression initially was accomplished by targeted ablation of the &#946 2m gene, however, this deletion also eliminates expression of non-classical MHC molecules including CD1d, Qa-2 and FcRn. Subsequently, NOD-cMHCI-/- mice were created using CRISPR/Cas9 technology to delete sequence in both classical MHC class I genes, H2-D1 and H2-K1. These mice do not express H2-D1b or H2-K1d. This strain, NOD-MHCI/II-/-, was created using CRISPR/Cas9 technology to generate a deletion in exon 2 of the MHC Class II H2-Ab1 (I-A) gene in the NOD-MHCI-/- strain. Mice homozygous for all three alleles lack expression of H2-Ab1g7, H2-K and H2-D. Thy1.2+ cells are reduced to 12% of total splenocytes and, of that subset, TCR&#945 &#946 + cells are reduced to 60% and with a corresponding increase in the percentage of TCR&#947 &#948 T cells. CD4+ T cells are reduced compared to NOD controls and NOD-MHCI-/-; CD8 T cells are reduced compared to NOD controls but increased as compared to NOD-MHCI-/-. At 9-12 weeks of age NOD-MHCI/II-/- mice are free of insulitis.
This strain is one of a series of mice that can be used to develop HLA-humanized NOD models for use in T1D therapy development.

The use of this mouse model is subject to the terms and conditions of the Limited Use Label License from Caribou Biosciences, Inc.

The use of this mouse strain or other product (the "Licensed Product") is subject to the terms and conditions of the Limited License from The Broad Institute.

This NOD-cMHCI/II-/- strain carries knock-out alleles for the classical MHC class I genes, H2-D1 and H2-K1, and the class II gene, H2-Ab1 (I-A). 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 T1D patients.

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

<a target="_blank" href="https://www.jax.org/jax-mice-and-services/customer-support" rel="noreferrer">Contact Customer Service</a> for more information.