title: Vascular lesions in mice with a deficit in Fas-mediated apoptosis and their transfer.
abstract: The lpr and gld genes are thought to result in an incapacity for Fas-mediated apoptosis of T and B cells and the development of subsequent autoimmune disease. A newly established gld-congenic strain of mice, MRL/MpTn-gld/gld (MRL/gld), was found to develop vascular lesions involving arteritis and glomerulonephritis (GN), which were similar to those observed in the MRL/Mp-lpr/lpr (MRL/lpr) strain. However, comparative studies with a C3H/HeJ strain bearing lpr or gld revealed that these lesions developed only in mice with an MRL background. We were successful in transferring GN to normal MHC-compatible gld/gld and irradiated +/+ mice by bone marrow cells of MRL/gld mice, but were unsuccessful using those of C3H/gld mice. Transfer of arteritis, however, was only successful in mice with an MRL background. Nephritogenic monoclonal antibodies obtained from an MRL/lpr and an MRL/gld mouse were shown to be bone marrow-derived and rich in clonal diversity, and at least two of these were capable of causing glomerular injury by different mechanisms. Development of GN and systemic arteritis in MRL/lpr and MRL/gld mice will be dependent not only on their incapacity for Fas-mediated apoptosis but also on bone marrow cells and peripheral cells with intrinsic defects.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nose
authors.forename: M R
authors.initials: MR
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Terasaki
authors.forename: M
authors.initials: M
authors.lastname: Miyazawa
authors.forename: S
authors.initials: S
authors.lastname: Mori
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D018014:Gene Transfer Techniques; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D026541:Heymann Nephritis Antigenic Complex; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology; D013625:Takayasu Arteritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019014:fas Receptor / Q000235:genetics*
chemical_list: D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D019014:fas Receptor