Improved Murine MHC-Deficient HLA Transgenic NOD Mouse Models for Type 1 Diabetes Therapy Development

Diabetes
Jeremy J RacineDavid V Serreze

Abstract

Improved mouse models for type 1 diabetes (T1D) therapy development are needed. T1D susceptibility is restored to normally resistant NOD.β2m-/- mice transgenically expressing human disease-associated HLA-A*02:01 or HLA-B*39:06 class I molecules in place of their murine counterparts. T1D is dependent on pathogenic CD8+ T-cell responses mediated by these human class I variants. NOD.β2m-/--A2.1 mice were previously used to identify β-cell autoantigens presented by this human class I variant to pathogenic CD8+ T cells and for testing therapies to attenuate such effectors. However, NOD.β2m-/- mice also lack nonclassical MHC I family members, including FcRn, required for antigen presentation, and maintenance of serum IgG and albumin, precluding therapies dependent on these molecules. Hence, we used CRISPR/Cas9 to directly ablate the NOD H2-Kd and H2-Db classical class I variants either individually or in tandem (cMHCI-/-). Ablation of the H2-Ag7 class II variant in the latter stock created NOD mice totally lacking in classical murine MHC expression (cMHCI/II-/-). NOD-cMHCI-/- mice retained nonclassical MHC I molecule expression and FcRn activity. Transgenic expression of HLA-A2 or -B39 restored pathogenic CD8+ T-cell development and ...Continue Reading

References

Aug 1, 1995·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·B D TaitL C Harrison
Jun 17, 1999·Nature Medicine·M A Atkinson, E H Leiter
Jun 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·F D ShiN Sarvetnick
Aug 8, 2001·The Journal of Experimental Medicine·B WangC R Wang
Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·E A JohnsonD V Serreze
Oct 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Michele P MarronDavid V Serreze
Feb 5, 2003·The Journal of Experimental Medicine·Chaity ChaudhuryClark L Anderson
Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Derry C RoopenianClark L Anderson
Jan 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yi-Guang ChenDavid V Serreze
Dec 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gabrielle G M PinkseBart O Roep
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiyuki TakakiDavid V Serreze
Oct 27, 2006·Diabetes·Qin OuyangConstadina Panagiotopoulos
Mar 1, 2007·Diabetes·Roberto MallonePeter van Endert
Mar 23, 2007·Annals of the New York Academy of Sciences·David V SerrezeTeresa P Dilorenzo
Mar 23, 2007·Annals of the New York Academy of Sciences·W W J UngerB O Roep
Aug 19, 2007·Nature Reviews. Immunology·Derry C Roopenian, Shreeram Akilesh
Nov 16, 2007·Nature·Sergey NejentsevUNKNOWN Wellcome Trust Case Control Consortium
Mar 25, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Irene JarchumTeresa P DiLorenzo
Jan 30, 2009·Diabetes, Obesity & Metabolism·J M M HowsonUNKNOWN Type 1 Diabetes Genetics Consortium
Dec 8, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Irene Jarchum, Teresa P DiLorenzo
Jul 1, 2010·Diabetes·Flemming PociotJørn Nerup
Aug 28, 2010·Diabetes·Janelle A NobleUNKNOWN Type 1 Diabetes Genetics Consortium
Oct 29, 2010·Expert Review of Clinical Immunology·Rodolfo José Chaparro, Teresa P Dilorenzo
Oct 18, 2011·European Journal of Immunology·Yannick SimoniAgnès Lehuen
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Janelle A Noble, Henry A Erlich
Dec 21, 2013·Diabetes·Christina L RoarkBrian M Freed
Aug 28, 2014·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jonathon T HillH Joseph Yost
Sep 16, 2014·Frontiers in Immunology·Kristi BakerRichard S Blumberg
May 11, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yi LiLi Wang
Oct 21, 2015·Nature Immunology·Dale I GodfreyD Branch Moody
Mar 1, 2016·Molecular and Cellular Therapies·Maja Thim LarsenKenneth A Howard
Feb 12, 2017·HLA : Immune Response Genetics·M-L MikkUNKNOWN Finnish Paediatric Diabetes Register

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Citations

Jul 4, 2018·Diabetes·Sandrine LuceChristian Boitard
Apr 7, 2019·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Abigail L D Tadenev, Robert W Burgess
Dec 11, 2019·PloS One·Colleen M ElsoStuart I Mannering
Apr 24, 2019·Diabetes·Anthony W PurcellTeresa P DiLorenzo
Aug 28, 2020·Drug Metabolism Reviews·Takeshi SusukidaKousei Ito
Nov 2, 2021·Frontiers in Immunology·Sandrine LuceChristian Boitard

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