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A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes

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 of murine major histocompatibility complex class I and class II, the murine insulin genes, and expresses as trans...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551915/
https://www.ncbi.nlm.nih.gov/pubmed/34721418
http://dx.doi.org/10.3389/fimmu.2021.748679
Descripción
Sumario: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 of murine major histocompatibility complex class I and class II, the murine insulin genes, and expresses as transgenes the HLA-A*02:01 allele, the diabetes high-susceptibility HLA-DQ8A and B alleles, the human insulin gene, and the human co-stimulatory molecule B7.1 in insulin-secreting cells. It develops spontaneous T1D along with CD4(+) and CD8(+) T-cell 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 autoimmune response to insulin-secreting cells in human T1D. It will allow evaluating peptide-based immunotherapy that may directly apply to T1D in human and complete preclinical model availability to address the issue of clinical heterogeneity of human disease.