NOD mice carrying only the HLA-A/H2-D/B2M transgene, commonly referred to as NOD.HHD, (Stock No. <a href="https://www.jax.org/strain/006604">006604</a>) develop significantly accelerated diabetes onset compared to NOD/ShiLtDvs (NOD) inbred mice.
This mutant stock is also homozygous for the B2mtm1Unc mutation which normally prevents the development of of CD8+ T cells. The presence of the transgene in the B2m-deficient background, however, restores CD8+ T cells, but at a significantly lower level than in NOD inbred mice. Due to the covalently linked nature of the B2M component encoded into the transgene, the transgenic construct is unable to rescue murine MHC class 1 molecules in the NOD.B2m deficient (Stock No. <a href="https://www.jax.org/strain/002309">002309</a>) mice. Thus, these double mutant mice only express human HLA-A2.1. Fifty-five percent of these NOD transgenic B2m-deficient mice develop diabetes by 30 weeks of age, while non-transgenic NOD.B2mtm1Unc do not develop diabetes. Insulitis scores assessed via histological examination of pancreata are similar between NOD/ShiLtDvs and NOD transgenic B2m-deficient mice. Although CD8+ T cell numbers in NOD transgenic B2m-deficient are lower than in NOD inbred mice, comparable numbers of CD8+ T cells can be cultured from pancreatic islets from both strains. The infiltrating T cells cultured from the double mutant islets are HLA-A2.1-specific, and are able to recognize islet specific antigens, such as IGRP.
NOD transgenic mice carrying the Prkdcscid (Stock No. <a href="https://www.jax.org/strain/006605">006605</a>) do not become diabetic.
This model provides humanized T cells that will be useful tools to identify MHC class I epitopes recognized by CD8+ T cells in type 1 diabetes patients and for testing new therapies focused on restoring immune tolerance.

These double mutant mice uniquely express human HLA-A2.1.

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

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