title: Expression of heterozygous lpr gene in MRL mice. II. Acceleration of glomerulonephritis, sialadenitis, and autoantibody production.
abstract: Recently we showed that not only homozygous MRL lpr/lpr mice but also heterozygous MRL +/lpr mice display defective antigen- and mitogen-driven T-cell responses as well as polyclonal B-cell activation compared with congeneic MRL +/+ mice. In this study we examined the impact of the heterozygous lpr gene on organ pathology in kidneys, joints, and salivary glands, as well as serum levels of immunoglobulins and autoantibodies in young and old MRL mice. Only 1 out of 17 heterozygous lpr-bearing MRL mice developed clinically overt renal disease with significant proteinuria and haematuria during the first year of life. However, examination of Ig and C3 deposits in glomeruli of kidneys from these mice revealed that the expression of the heterozygous lpr gene in MRL mice accelerates glomerulonephritis. In addition, histological examination of the submandibular salivary glands showed an increased focus score in heterozygous MRL mice at 4-5 months of age compared with that of matched congeneic +/+ mice. In contrast, no signs of arthropathy were registered in the heterozygous lpr-bearing MRL mice. Heterozygous MRL mice displayed an expanding lymphoid system as evaluated by significantly increased spleen and lymph node weights compared with those of matched MRL +/+ mice. Further evidence for immunomodulatory properties of the heterozygous lpr gene was obtained when analysing serum levels of IgG, IgM, and autoantibodies. Thus, heterozygous MRL +/lpr mice produced significantly higher levels of both Ig and autoantibodies than matched MRL +/+ mice. We conclude that the expression of the heterozygous lpr gene in MRL mice results in acceleration of the autoimmune process, giving rise to precocious clinical disease.
authors.affiliation: Department of Medical Microbiology, University of Göteborg, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Carlsten
authors.forename: A
authors.initials: A
authors.lastname: Tarkowski
authors.forename: R
authors.initials: R
authors.lastname: Jonsson
authors.forename: L A
authors.initials: LA
authors.lastname: Nilsson
mesh_terms: D000367:Age Factors; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology*; D006579:Heterozygote; D007136:Immunoglobulins / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D051379:Mice; D012466:Salivary Gland Diseases / Q000209:etiology*; D012793:Sialadenitis / Q000209:etiology*; D013585:Synovitis / Q000209:etiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007136:Immunoglobulins