title: Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis.
abstract: Mast cells are a critical component of allergic responses in humans, and animal models that allow the in vivo investigation of their contribution to allergy and evaluation of new human-specific therapeutics are urgently needed.
  
  
  
  To develop a new humanized mouse model that supports human mast cell engraftment and human IgE-dependent allergic responses.
  
  
  
  This model is based on the NOD-scid IL2rg(null)SCF/GM-CSF/IL3 (NSG-SGM3) strain of mice engrafted with human thymus, liver, and hematopoietic stem cells (termed Bone marrow, Liver, Thymus [BLT]).
  
  
  
  Large numbers of human mast cells develop in NSG-SGM3 BLT mice and populate the immune system, peritoneal cavity, and peripheral tissues. The human mast cells in NSG-SGM3 BLT mice are phenotypically similar to primary human mast cells and express CD117, tryptase, and FcεRI. These mast cells undergo degranulation in an IgE-dependent and -independent manner, and can be readily cultured in vitro for additional studies. Intradermal priming of engrafted NSG-SGM3 mice with a chimeric IgE containing human constant regions resulted in the development of a robust passive cutaneous anaphylaxis response. Moreover, we describe the first report of a human mast cell antigen-dependent passive systemic anaphylaxis response in primed mice.
  
  
  
  NSG-SGM3 BLT mice provide a readily available source of human mast cells for investigation of mast cell biology and a preclinical model of passive cutaneous anaphylaxis and passive systemic anaphylaxis that can be used to investigate the pathogenesis of human allergic responses and to test new therapeutics before their advancement to the clinic.
authors.affiliation: Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
authors.affiliation: Allakos Inc, San Carlos, Ill.
authors.forename: Rustom
authors.initials: R
authors.lastname: Falahati
authors.affiliation: Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Mass.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Kenney
authors.affiliation: Allakos Inc, San Carlos, Ill.
authors.forename: John
authors.initials: J
authors.lastname: Leung
authors.affiliation: Allakos Inc, San Carlos, Ill.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bebbington
authors.affiliation: Allakos Inc, San Carlos, Ill.
authors.forename: Nenad
authors.initials: N
authors.lastname: Tomasevic
authors.affiliation: Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Krier
authors.affiliation: Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Jackson Laboratory, Bar Harbor, Me.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Mass.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Mass. Electronic address: michael.brehm@umassmed.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brehm
mesh_terms: D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D016031:Liver Transplantation; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation
chemical_list: D007073:Immunoglobulin E
keywords: Mast cell; NSG; NSG-SGM3; PCA; PSA; humanized mice; passive cutaneous anaphylaxis; passive systemic anaphylaxis