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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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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
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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
author_facet 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
author_sort Luce, Sandrine
collection PubMed
description 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.
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spelling pubmed-85519152021-10-29 A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes 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 Front Immunol Immunology 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. Frontiers Media S.A. 2021-10-14 /pmc/articles/PMC8551915/ /pubmed/34721418 http://dx.doi.org/10.3389/fimmu.2021.748679 Text en Copyright © 2021 Luce, Guinoiseau, Gadault, Letourneur, Nitschke, Bras, Vidaud, Charneau, Larger, Colli, Eizirik, Lemonnier and Boitard https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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
A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
title A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
title_full A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
title_fullStr A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
title_full_unstemmed A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
title_short A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
title_sort humanized mouse strain that develops spontaneously immune-mediated diabetes
topic Immunology
url 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
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