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Article Dans Une Revue Diabetes Année : 2018

Humanized Mouse Model to Study Type 1 Diabetes

Sandrine Luce
  • Fonction : Auteur
Sophie Guinoiseau
  • Fonction : Auteur
Alexis Gadault
  • Fonction : Auteur
Franck Letourneur
  • Fonction : Auteur
Bertrand Blondeau
Patrick Nitschke
  • Fonction : Auteur
Eric Pasmant
Michel Vidaud
  • Fonction : Auteur
François Lemonnier
  • Fonction : Auteur
Christian Boitard

Résumé

Key requirements in type 1 diabetes (T1D) are in setting up new assays as diagnostic biomarkers that will apply to prediabetes, likely T-cell assays, and in designing antigen-specific therapies to prevent T1D development. New preclinical models of T1D will be required to help with advancing both aims. By crossing mouse strains that lack either murine MHC class I and class II genes and insulin genes, we developed YES mice that instead express human HLA-A*02:01, HLA-DQ8, and insulin genes as transgenes. The metabolic and immune phenotype of YES mice is basically identical to that of the parental strains. YES mice remain insulitis and diabetes free up to 1 year of follow-up, maintain normoglycemia to an intraperitoneal glucose challenge in the long-term range, have a normal β-cell mass, and show normal immune responses to conventional antigens. This new model has been designed to evaluate adaptive immune responses to human insulin on a genetic background that recapitulates a human high-susceptibility HLA-DQ8 genetic background. Although insulitis free, YES mice develop T1D when challenged with polyinosinic-polycytidylic acid. They allow the characterization of preproinsulin epitopes recognized by CD8+ and CD4+ T cells upon immunization against human preproinsulin or during diabetes development.

Dates et versions

hal-03972793 , version 1 (03-02-2023)

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Citer

Sandrine Luce, Sophie Guinoiseau, Alexis Gadault, Franck Letourneur, Bertrand Blondeau, et al.. Humanized Mouse Model to Study Type 1 Diabetes. Diabetes, 2018, 67 (9), pp.1816-1829. ⟨10.2337/db18-0202⟩. ⟨hal-03972793⟩
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