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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8551915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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