Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 Mar 1;161(3):602–616. doi: 10.1084/jem.161.3.602

Abnormalities induced by the mutant gene, lpr. Patterns of disease and expression of murine leukemia viruses in SJL/J mice homozygous and heterozygous for lpr

PMCID: PMC2187576  PMID: 2982991

Abstract

SJL/J mice heterozygous or homozygous for the lpr mutation were compared with SJL/J-+/+ mice for longevity, histopathology, antigenic characteristics of lymphocytes and expression of murine leukemia viruses (MuLV). In comparison to +/+ mice, lpr homozygotes had a markedly shortened life span, died with infiltrative pulmonary disease, but little or no renal disease, and expressed high levels of infectious ecotropic MuLV in lymphoid tissues. SJL-lpr/+ mice had a life span intermediate between SJL-+/+ and -lpr/lpr mice, died with lymphomas that histologically resembled the neoplasms of +/+ mice, and sometimes expressed high levels of ecotropic MuLV. The lymphomas of lpr/+ could be transplanted to +/+ recipients in 78% of cases, and continuous in vitro lines were established from some of them. Similar effects on virus expression or lymphoma development were not observed in other strains homozygous or heterozygous for the lpr mutation. These results indicate that the diseases expressed by mice homozygous for the lpr mutation are highly strain-dependent, and that this gene can have an effect in the heterozygous state in SJL mice.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman A., Theofilopoulos A. N., Weiner R., Katz D. H., Dixon F. J. Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2. J Exp Med. 1981 Sep 1;154(3):791–808. doi: 10.1084/jem.154.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chan H. W., Bryan T., Moore J. L., Staal S. P., Rowe W. P., Martin M. A. Identification of ecotropic proviral sequences in inbred mouse strains with a cloned subgenomic DNA fragment. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5779–5783. doi: 10.1073/pnas.77.10.5779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cloyd M. W., Hartley J. W., Rowe W. P. Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. J Exp Med. 1980 Mar 1;151(3):542–552. doi: 10.1084/jem.151.3.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Colombatti A., Hughes E. N., Taylor B. A., August J. T. Gene for a major cell surface glycoprotein of mouse macrophages and other phagocytic cells is on chromosome 2. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1926–1929. doi: 10.1073/pnas.79.6.1926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davidson W. F., Morse H. C., 3rd, Mathieson B. J., Kozak C. A., Shen F. W. The B cell alloantigen Ly-17.1 is controlled by a gene closely linked to Ly-20 and Ly-9 on chromosome 1. Immunogenetics. 1983;17(3):325–329. doi: 10.1007/BF00364416. [DOI] [PubMed] [Google Scholar]
  7. Davidson W. F., Roths J. B., Holmes K. L., Rudikoff E., Morse H. C., 3rd Dissociation of severe lupus-like disease from polyclonal B cell activation and IL 2 deficiency in C3H-lpr/lpr mice. J Immunol. 1984 Aug;133(2):1048–1056. [PubMed] [Google Scholar]
  8. Dumont F. J., Habbersett R. C., Nichols E. A., Treffinger J. A., Tung A. S. A monoclonal antibody (100C5) to the Lyt-2-T cell population expanding in MRL/Mp-lpr/lpr mice detects a surface antigen normally expressed on Lyt-2+ cells and B cells. Eur J Immunol. 1983 Jun;13(6):455–459. doi: 10.1002/eji.1830130605. [DOI] [PubMed] [Google Scholar]
  9. Ford R. J., Ruppert B., Maizel A. L. SJL tumor: a neoplasm involving macrophages. Lab Invest. 1981 Aug;45(2):111–119. [PubMed] [Google Scholar]
  10. Fredrickson T. N., Morse H. C., 3rd, Rowe W. P. Spontaneous tumors of NFS mice congenic for ecotropic murine leukemia virus induction loci. J Natl Cancer Inst. 1984 Aug;73(2):521–524. doi: 10.1093/jnci/73.2.521. [DOI] [PubMed] [Google Scholar]
  11. Hang L., Theofilopoulos A. N., Dixon F. J. A spontaneous rheumatoid arthritis-like disease in MRL/l mice. J Exp Med. 1982 Jun 1;155(6):1690–1701. doi: 10.1084/jem.155.6.1690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Izui S., Kelley V. E., Masuda K., Yoshida H., Roths J. B., Murphy E. D. Induction of various autoantibodies by mutant gene lpr in several strains of mice. J Immunol. 1984 Jul;133(1):227–233. [PubMed] [Google Scholar]
  13. Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J Virol. 1982 Jul;43(1):26–36. doi: 10.1128/jvi.43.1.26-36.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Katz I. R., Asofsky R., Thorbecke G. J. Suppression of spontaneous reticulum cell sarcoma development and of syngeneic stimulator cell by anti-mu treatment of SJL/J mice. J Immunol. 1980 Sep;125(3):1355–1359. [PubMed] [Google Scholar]
  15. Kelley V. E., Roths J. B. Increase in macrophage Ia expression in autoimmune mice: role of the Ipr gene. J Immunol. 1982 Sep;129(3):923–925. [PubMed] [Google Scholar]
  16. Lander M. R., Moll B., Rowe W. P. A procedure for culture of cells from mouse tail biopsies: brief communication. J Natl Cancer Inst. 1978 Feb;60(2):477–478. [PubMed] [Google Scholar]
  17. Langdon W. Y., Theodore T. S., Buckler C. E., Stimpfling J. H., Martin M. A., Morse H. C., 3rd Relationship between a retroviral germ line reintegration and a new mutation at the ashen locus in B10.F mice. Retroviral integration and an ashen mutation. Virology. 1984 Feb;133(1):183–190. doi: 10.1016/0042-6822(84)90437-9. [DOI] [PubMed] [Google Scholar]
  18. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  19. Lerman S. P., Carswell E. A., Chapman J., Thorbecke G. J. Properties of reticulum cell sarcomas in SJL/J mice. III. Promotion of tumor growth in irradiated mice by normal lymphoid cells. Cell Immunol. 1976 Apr;23(1):53–67. doi: 10.1016/0008-8749(76)90171-4. [DOI] [PubMed] [Google Scholar]
  20. Lewis D. E., Giorgi J. V., Warner N. L. Flow cytometry analysis of T cells and continuous T-cell lines from autoimmune MRL/l mice. Nature. 1981 Jan 22;289(5795):298–300. doi: 10.1038/289298a0. [DOI] [PubMed] [Google Scholar]
  21. Lu C. Y., Unanue E. R. Spontaneous T-cell lymphokine production and enhanced macrophage Ia expression and tumoricidal activity in MRL-lpr mice. Clin Immunol Immunopathol. 1982 Nov;25(2):213–222. doi: 10.1016/0090-1229(82)90184-2. [DOI] [PubMed] [Google Scholar]
  22. McIntire K. R., Law L. W. Abnormal serum immunoglobulins occurring with reticular neoplasms in a inbred strain of mouse. J Natl Cancer Inst. 1967 Dec;39(6):1197–1211. [PubMed] [Google Scholar]
  23. Morse H. C., 3rd, Chused T. M., Boehm-Truitt M., Mathieson B. J., Sharrow S. O., Hartley J. W. XenCSA: cell surface antigens related to the major glycoproteins (gp70) of xenotropic murine leukemia viruses. J Immunol. 1979 Feb;122(2):443–454. [PubMed] [Google Scholar]
  24. Morse H. C., 3rd, Davidson W. F., Yetter R. A., Murphy E. D., Roths J. B., Coffman R. L. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol. 1982 Dec;129(6):2612–2615. [PubMed] [Google Scholar]
  25. Mountz J. D., Steinberg A. D., Klinman D. M., Smith H. R., Mushinski J. F. Autoimmunity and increased c-myb transcription. Science. 1984 Nov 30;226(4678):1087–1089. doi: 10.1126/science.6494925. [DOI] [PubMed] [Google Scholar]
  26. Pattengale P. K., Frith C. H. Immunomorphologic classification of spontaneous lymphoid cell neoplasms occurring in female BALB/c mice. J Natl Cancer Inst. 1983 Jan;70(1):169–179. [PubMed] [Google Scholar]
  27. Potter M., Hartley J. W., Wax J. S., Gallahan D. Effect of MuLV-related genes on plasmacytomagenesis in BALB/c mice. J Exp Med. 1984 Aug 1;160(2):435–440. doi: 10.1084/jem.160.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roths J. B., Murphy E. D., Eicher E. M. A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J Exp Med. 1984 Jan 1;159(1):1–20. doi: 10.1084/jem.159.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scheid M. P., Landreth K. S., Tung J. S., Kincade P. W. Preferential but nonexclusive expression of macromolecular antigens on B-lineage cells. Immunol Rev. 1982;69:141–159. doi: 10.1111/j.1600-065x.1983.tb00453.x. [DOI] [PubMed] [Google Scholar]
  30. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  31. Steinberg A. D., Roths J. B., Murphy E. D., Steinberg R. T., Raveche E. S. Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/lpr mice. J Immunol. 1980 Aug;125(2):871–873. [PubMed] [Google Scholar]
  32. Theofilopoulos A. N., Balderas R. S., Shawler D. L., Lee S., Dixon F. J. Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice. J Exp Med. 1981 Jun 1;153(6):1405–1414. doi: 10.1084/jem.153.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Theofilopoulos A. N., Dixon F. J. Etiopathogenesis of murine SLE. Immunol Rev. 1981;55:179–216. doi: 10.1111/j.1600-065x.1981.tb00343.x. [DOI] [PubMed] [Google Scholar]
  34. Theofilopoulos A. N., Eisenberg R. A., Bourdon M., Crowell J. S., Jr, Dixon F. J. Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med. 1979 Feb 1;149(2):516–534. doi: 10.1084/jem.149.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
  36. Wanebo H. J., Gallmeier W. M., Boyse E. A., Old L. J. Paraproteinemia and reticulum cell sarcoma in an inbred mouse strain. Science. 1966 Nov 18;154(3751):901–903. doi: 10.1126/science.154.3751.901. [DOI] [PubMed] [Google Scholar]
  37. Wofsy D., Murphy E. D., Roths J. B., Dauphinée M. J., Kipper S. B., Talal N. Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene. J Exp Med. 1981 Nov 1;154(5):1671–1680. doi: 10.1084/jem.154.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES