title: Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2.
abstract: Thymectomy on day 3 after birth induced autoimmune gastritis (AIG) at the age of 2 months in 51-73% of BALB/c mice, and in only 3-5% of DBA/2 mice. AIG was detected by histological and serological (immunofluorescence staining for detecting anti-parietal cell autoantibody) examination. However, autoantibody was weakly positive in almost all of these DBA/2 mice when measured by ELISA using extract of murine gastric mucosa as the antigen. To investigate genetically the mechanism controlling the incidence of AIG, II recombinant inbred strains established by brother-sister mating of (BALB/c x DBA/2) F2 mice (C x D2 strains) were used. Among 26 markers tested, the Mls-1 locus on BALB/c chromosome 1 and the Hc locus coding a complement component (C5) on BALB/c chromosome 2 were found to be associated with high susceptibility to AIG. However, if one or both of the loci were of DBA/2 origin, mice showed medium or low susceptibility to AIG. For further analysis, F1, F2 and back-cross generations of these two strains were tested, but segregation of a single susceptibility or insusceptibility gene was not obtained. Taken together, it seems probable that two or more genes are involved in the induction mechanism of AIG. We did not detect C5 deposition in AIG lesions, nor complement-dependent cytotoxic antibody to parietal cells in serum from AIG mice. However, injection of irradiated spleen cells of DBA/2 mice into BALB/c mice thymectomized on day 3 augmented the incidence of AIG from 71 to 100%, but not that of oophoritis (33%). A relationship between Mls-1a determinants and the pathogenesis of AIG was further suggested from the fact that V beta 6 TcR-expressing T cells increased in number in AIG-bearing compared with normal BALB/c mice.
authors.affiliation: Department of Immunobiology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Hosono
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: K
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: R
authors.initials: R
authors.lastname: Kannagi
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Okuma
authors.forename: T
authors.initials: T
authors.lastname: Masuda
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics*; D002875:Chromosomes; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013934:Thymectomy
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell