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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.748679/full |
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| author | Sandrine Luce Sandrine Luce Sophie Guinoiseau Sophie Guinoiseau Alexis Gadault Alexis Gadault Franck Letourneur Patrick Nitschke Marc Bras Michel Vidaud Pierre Charneau Etienne Larger Etienne Larger Maikel L. Colli Decio L. Eizirik Decio L. Eizirik François Lemonnier François Lemonnier Christian Boitard Christian Boitard Christian Boitard |
| author_facet | Sandrine Luce Sandrine Luce Sophie Guinoiseau Sophie Guinoiseau Alexis Gadault Alexis Gadault Franck Letourneur Patrick Nitschke Marc Bras Michel Vidaud Pierre Charneau Etienne Larger Etienne Larger Maikel L. Colli Decio L. Eizirik Decio L. Eizirik François Lemonnier François Lemonnier Christian Boitard Christian Boitard Christian Boitard |
| author_sort | Sandrine Luce |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:35:18Z |
| format | Article |
| id | doaj.art-6206b24d7ab14e419c5c8a08cad4d3d1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T03:35:18Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6206b24d7ab14e419c5c8a08cad4d3d12022-12-21T20:37:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.748679748679A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated DiabetesSandrine Luce0Sandrine Luce1Sophie Guinoiseau2Sophie Guinoiseau3Alexis Gadault4Alexis Gadault5Franck Letourneur6Patrick Nitschke7Marc Bras8Michel Vidaud9Pierre Charneau10Etienne Larger11Etienne Larger12Maikel L. Colli13Decio L. Eizirik14Decio L. Eizirik15François Lemonnier16François Lemonnier17Christian Boitard18Christian Boitard19Christian Boitard20Laboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceMedical Faculty, Paris University, Paris, FranceLaboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceMedical Faculty, Paris University, Paris, FranceLaboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceMedical Faculty, Paris University, Paris, FranceLaboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceMedical Faculty, Paris University, Paris, FranceMedical Faculty, Paris University, Paris, FranceBiochemistry and Molecular Genetics Department, Cochin Hospital, Paris, FranceMolecular Virology and Vaccinology, Pasteur Institute, Paris, FranceLaboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceDiabetology Department, Cochin Hospital, Paris, FranceUniversité Libre de Bruxelles (ULB) Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, BelgiumUniversité Libre de Bruxelles (ULB) Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, BelgiumDiabetes Center, Indiana Biosciences Research Institute (IBRI), Indianapolis, IN, United StatesLaboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceMedical Faculty, Paris University, Paris, FranceLaboratory Immunology of Diabetes, INSERMU1016, Department EMD, Cochin Institute, Paris, FranceMedical Faculty, Paris University, Paris, FranceDiabetology Department, Cochin Hospital, Paris, FranceTo 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.748679/fullautoimmunitytype 1 diabetes (T1D)humanized mouseHLA-DQ8epitopespreproinsulin |
| spellingShingle | Sandrine Luce Sandrine Luce Sophie Guinoiseau Sophie Guinoiseau Alexis Gadault Alexis Gadault Franck Letourneur Patrick Nitschke Marc Bras Michel Vidaud Pierre Charneau Etienne Larger Etienne Larger Maikel L. Colli Decio L. Eizirik Decio L. Eizirik François Lemonnier François Lemonnier Christian Boitard Christian Boitard Christian Boitard A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes Frontiers in Immunology autoimmunity type 1 diabetes (T1D) humanized mouse HLA-DQ8 epitopes preproinsulin |
| 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 | autoimmunity type 1 diabetes (T1D) humanized mouse HLA-DQ8 epitopes preproinsulin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.748679/full |
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