Summary
Recombinant inbred (RI) lines were established from (MRL/lpr × AKR) crosses in order to analyze the role of thelpr gene and the particiption of background genes in the lymphoproliferation and the development of lupus glomerulonephritis (LGN). In this study, six lines were used to compare with MRL/lpr and AKR mice. Lymphadenopathy was pressent in four lines (A-22, A-31 b, A-31 e and C-12) but absent in the other two (A-21 and C-21). The degree of lymphoproliferation varied between individuals of the RI lines showing lymphadenopathy. On gross examinations, the most marked lymph node enlargement was seen in the A-31 b line, which resembled MRL/lpr mice in this respect; lymphadenopathy was least prominent in the C-12 line and intermediate degrees occurred in the A-22 and A-31 e lines. Like MRL/lpr mice, deaths in the RI lines were due to LGN; however, in the lines with lymphadenopathy, 50% mortalities occurred a few weeks later than in MRL/lpr mice. The kidneys were examined histologically for proliferative, exudative, extracapillary and membranous changes in the glomeruli. The glomerular lesions in the A-22, A-31 b and A-31 e lines closely resembled those in MRL/lpr mice, but in the C12 line in which lymph node enlargement was least apparent, the histological abnormalities were significantly more severe. Of the lines without lymphadenopathy, histopathological examination showed obvious renal abnormalities in the A-21 line but none in the C-21 line or in AKR mice. From these findings it appears that there are autosomal genes which affect the expression of thelpr gene and thus modify the development of LGN and lymphoproliferation.
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Andrews BA, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED′, Roths JB, Dixon FJ (1978) Spontaneous murine lupus-like syndroms. Clinical and immunopathological manifestations in several strains. J Exp Med 148:1198–1215
Davidson WF, Dumont FJ, Bedigian HG, Fowlkes BJ, Morse III HC (1986) Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gldmice. J Immunol 136:4075–4084
Fujiwara M, Kariyone A, Shiraki M (1985) Studies on the role of thelpr gene in the development of immunological abnormalities and lupus nephritis. Analyses in F2 mice. Clin Exp Immunol 59:161–168
Izui S, Kelley VE, Masuda K, Yoshida H, Roths JB, Murphy ED (1984) Induction of various autoantibodies by mutant genelpr in several strains of mice. J Immunol 133:227–233
Katagiri T, Nakano T, Ueno K, Ohsugi Y, Fujiwara M (1985) Activities of a soluble extract from lymphoid cells of MRL mice. Effect on B cell differentiation in vitro. Int Arch Allergy Appl Immunol 78:233–236
Kelley VE, Roths JB (1985) Interaction of mutantlpr gene with background strain influences renal disease. Clin Immunol Immunopathol 37:220–229
Makino M, Fujiwara M, Watanabe H (1987) Studies on the mechanisms of the development of lupus nephritis in BXSB mice. I. Analyses of immunological abnormalities at the onset period. J Clin Lab Immunol 22:127–131
Morse III HC, Davidson WF, Yetter RA, Murphy ED, Roths JB, Coffmann RL (1982) Abnormalities induced by the mutant genelpr: expansion of a unique lymphocyte subset. J Immunol 129:2612–2615
Morse III HC, Roths JB, Davidson WF, Langdon WY, Fredrickson TN, Hartley JW (1985) Abnormalities induced by the mutant gene,lpr. Patterns of disease and expression of murine leukemia viruses in SJL/J mice homozygous and heterozygous forlpr. J Exp Med 161:602–616
Murphy ED, Roths JB (1987) Autoimmunity and lymphoproliferation: Induction by mutant gnelpr and acceleration by a maleassociated factor in strain BXSB mice. In: Genetic control of autoimmune disease. Elsevier-North-Holland, New York, pp 207–221
Nemazee DA, Studer S, Steinmetz M, Dembic Z, Kiefer M (1985) The lymphoproliferating cells of MRL-lpr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen. Eur J Immuno 15:760–764
Prud’Homme GJ, Park CL, Fieser TM, Kofier R, Dixon FJ, Theofilopoulos AN (1983) Identification of a B cell diffrentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of thelpr/lpr genotype. J Exp Med 157:730–742
Raveche ES, Novotny EA, Hansen CT, Tjio JH, Steinberg AD (1981) Genetic studies in NZB mice. V. Recombinant inbred lines demonstrate that separate genes control autoimmune phenotype. J Exp Med 153:1187–1197
Roths JB, Murphy ED, Izui S, Kelley V (1983) Modification of expression oflpr by background genome. Fed Proc (Abstr) 40:1075
Theofilopoulos AN, Dixon FJ (1981) Etiopathogenesis of murine SLE. Immunol Rev 55:179–216
Theofilopoulos AN, Dixon FJ (1985) Murine models of systemic lupus erythematosus. Adv Immunol 37:269–390
Theofilopoulos AN, Eisenberg RA, Bourdon JS, Crowell JR, Dixon FJ (1979) Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med 149:516–534
Warren RW, Caster SA, Roths JB, Murphy ED, Pisetsky DS (1984) The influence of thelpr gene on B cell activation: differential antibody expression inlpr congenic mouse strains. Clin Immunol Immunopathol 31:65–77
Wofsy D, Hardy RR, Seaman W (1984) The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on “helper” T cells that is involved in the response to class II major histocompatibility antigens. J Immunol 132:2686–2689
Wofsy D, Murphy ED, Roths JB, Dauphinie MJ, Kipper SB, Talal N (1981) Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing thelpr gene. J Exp Med 154:1671–1680
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Makino, M., Morita, T. & Fujiwara, M. Histopathological characteristics of the kidney in recombinant inbred mice established from MRL/lpr × AKR crossing. Virchows Archiv B Cell Pathol 56, 59–65 (1988). https://doi.org/10.1007/BF02890002
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DOI: https://doi.org/10.1007/BF02890002