title: A new mouse model of autoimmune ocular myasthenia gravis.
abstract: OBJECTIVE
  To establish a novel model of autoimmune ocular myasthenia gravis (oMG) in mice and study the pathogenic mechanisms of oMG.
  
  
  METHODS
  oMG was induced in HLA-DQ8 transgenic, HLA-DR3 transgenic, major histocompatibility complex (MHC) class II-deficient, C57BL/6, and C57BL/10 mice by immunization with an Escherichia coli plasmid expressing the recombinant human acetylcholine receptor (AChR) alpha subunit.
  
  
  RESULTS
  All strains of immunized mice developed ocular myasthenia gravis with varying disease incidence and severity. HLA-DQ8 transgenic mice were highly susceptible to oMG. Mice with oMG had serum autoantibodies to the mouse extraocular AChR, pathologic deposits of IgG, C3, and C5b-C9 in their extraocular and limb neuromuscular junctions, and droopiness of eyelids. HLA-DR3 transgenic and MHC class II-deficient mice were relatively resistant to oMG induced by AChR alpha subunit immunization and had minimal ocular abnormalities.
  
  
  CONCLUSIONS
  These findings suggest that oMG pathogenesis could be triggered by immunity to the human AChR alpha subunit and that MHC class II molecule is required for human AChR alpha subunit presentation and CD4 cell-mediated anti-AChR antibody class switching. Differential oMG susceptibility observed in DQ8 and DR3 transgenic mice correlated with the intensity of lymphocytes to respond to the human AChR alpha subunit. This new model of oMG will be a valuable tool for studying the mechanism of oMG and gMG pathogenesis in humans and for preclinical therapeutic analysis.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas medical Branch, Galveston, TX 77555-1070, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
authors.forename: Shamsher S
authors.initials: SS
authors.lastname: Saini
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Windy
authors.initials: W
authors.lastname: Allman
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
authors.forename: Tian Lin
authors.initials: TL
authors.lastname: Xiao
authors.forename: Premkumar
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003176:Complement C3 / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006683:HLA-DQ Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D015835:Ocular Motility Disorders / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D010957:Plasmids; D011863:Radioimmunoassay; D011978:Receptors, Nicotinic / Q000276:immunology
chemical_list: D003176:Complement C3; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015803:HLA-DR3 Antigen; D011978:Receptors, Nicotinic