AUTHOR=Luce Sandrine , Guinoiseau Sophie , Gadault Alexis , Letourneur Franck , Nitschke Patrick , Bras Marc , Vidaud Michel , Charneau Pierre , Larger Etienne , Colli Maikel L. , Eizirik Decio L. , Lemonnier François , Boitard Christian 

TITLE=A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.748679

DOI=10.3389/fimmu.2021.748679

ISSN=1664-3224

ABSTRACT=To circumvent the limitations of available preclinical models for the study of type 1 diabetes (T1D), we developed a new humanized model, the YES-RIP-hB7.1 mouse. This mouse is deficient for murine major histocompatibility complex class I and class II, the murine insulin genes and expresses as transgene the HLA-A*02:01allele, the diabetes high susceptibility HLA-DQ8A and B alleles, the human insulin gene and, in insulin-secreting cells, the human co-stimulatory molecule B7.1. It develops spontaneous T1D along with CD4+ and CD8+ T-cells responses to human preproinsulin epitopes. Most of the responses identified in these mice were validated in T1D patients. This model is amenable to characterization of hPPI-specific epitopes involved in T1D and to the identification of factors that may trigger the autoimmune response to insulin-secreting cells in human T1D. It will allow evaluating peptide-based immunotherapy that may directly apply to T1D in the human and complete preclinical model availability to address the issue of the clinical heterogeneity of the human disease.