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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Feb 1;171(2):519–531. doi: 10.1084/jem.171.2.519

A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse

PMCID: PMC2187722  PMID: 2406366

Abstract

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He- gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H- lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.

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Selected References

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  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. Davidson W. F., Dumont F. J., Bedigian H. G., Fowlkes B. J., Morse H. C., 3rd Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J Immunol. 1986 Jun 1;136(11):4075–4084. [PubMed] [Google Scholar]
  4. Davidson W. F., Holmes K. L., Roths J. B., Morse H. C., 3rd Immunologic abnormalities of mice bearing the gld mutation suggest a common pathway for murine nonmalignant lymphoproliferative disorders with autoimmunity. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1219–1223. doi: 10.1073/pnas.82.4.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davignon J. L., Cohen P. L., Eisenberg R. A. Rapid T cell receptor modulation accompanies lack of in vitro mitogenic responsiveness of double negative T cells to anti-CD3 monoclonal antibody in MRL/Mp-lpr mice. J Immunol. 1988 Sep 15;141(6):1848–1854. [PubMed] [Google Scholar]
  6. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  7. Dumont F. J., Coker L. Z., Habbersett R. C., Treffinger J. A. Xenogeneic monoclonal antibody to an Ly-6-linked murine cell surface antigen: differential reactivity with T cell subpopulations and bone marrow cells. J Immunol. 1985 Apr;134(4):2357–2365. [PubMed] [Google Scholar]
  8. Glasebrook A. L., Sarmiento M., Loken M. R., Dialynas D. P., Quintans J., Eisenberg L., Lutz C. T., Wilde D., Fitch F. W. Murine T lymphocyte clones with distinct immunological functions. Immunol Rev. 1981;54:225–266. doi: 10.1111/j.1600-065x.1981.tb00439.x. [DOI] [PubMed] [Google Scholar]
  9. Hashimoto Y., Maxam A. M., Greene M. I. T-cell antigen-receptor genes in autoimmune mice. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7865–7869. doi: 10.1073/pnas.83.20.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jachez B., Montecino-Rodriguez E., Fonteneau P., Loor F. Partial expression of the lpr locus in the heterozygous state: presence of autoantibodies. Immunology. 1988 May;64(1):31–36. [PMC free article] [PubMed] [Google Scholar]
  11. Kanai Y., Tauchi M., Aotsuka S., Yokohari R. A simple and rapid microenzyme-linked immunosorbent assay for antibodies to poly(ADP-ribose) in systemic lupus erythematosus. J Immunol Methods. 1982 Sep 30;53(3):355–365. doi: 10.1016/0022-1759(82)90182-x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Mountz J. D., Huppi K. E., Seldin M. F., Mushinski J. F., Steinberg A. D. T cell receptor gene expression in autoimmune mice. J Immunol. 1986 Aug 1;137(3):1029–1036. [PubMed] [Google Scholar]
  14. Mountz J. D., Mushinski J. F., Mark G. E., Steinberg A. D. Oncogene expression in autoimmune mice. J Mol Cell Immunol. 1985;2(3):121–131. [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Seldin M. F., Morse H. C., 3rd, Reeves J. P., Scribner C. L., LeBoeuf R. C., Steinberg A. D. Genetic analysis of autoimmune gld mice. I. Identification of a restriction fragment length polymorphism closely linked to the gld mutation within a conserved linkage group. J Exp Med. 1988 Feb 1;167(2):688–693. doi: 10.1084/jem.167.2.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Seldin M. F., Reeves J. P., Scribner C. L., Roths J. B., Davidson W. F., Morse H. C., 3rd, Steinberg A. D. Effect of xid on autoimmune C3H-gld/gld mice. Cell Immunol. 1987 Jun;107(1):249–255. doi: 10.1016/0008-8749(87)90284-x. [DOI] [PubMed] [Google Scholar]
  19. Shlomchik M. J., Marshak-Rothstein A., Wolfowicz C. B., Rothstein T. L., Weigert M. G. The role of clonal selection and somatic mutation in autoimmunity. 1987 Aug 27-Sep 2Nature. 328(6133):805–811. doi: 10.1038/328805a0. [DOI] [PubMed] [Google Scholar]
  20. Singer P. A., McEvilly R. J., Noonan D. J., Dixon F. J., Theofilopoulos A. N. Clonal diversity and T-cell receptor beta-chain variable gene expression in enlarged lymph nodes of MRL-lpr/lpr lupus mice. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7018–7022. doi: 10.1073/pnas.83.18.7018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith H. R., Steinberg A. D. Autoimmunity--a perspective. Annu Rev Immunol. 1983;1:175–210. doi: 10.1146/annurev.iy.01.040183.001135. [DOI] [PubMed] [Google Scholar]
  22. Tanaka S., Matsuzawa A., Kato H., Esaki K., Sudo K., Yamanouchi K. Inbred strains of mice maintained at the Institute of Medical Science, University of Tokyo. Jpn J Exp Med. 1987 Aug;57(4):241–245. [PubMed] [Google Scholar]
  23. Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]
  24. Yui K., Wadsworth S., Yellen A., Hashimoto Y., Kokai Y., Greene M. I. Molecular and functional properties of novel T cell subsets in C3H-gld/gld and nude mice. Implications for thymic and extrathymic maturation. Immunol Rev. 1988 Aug;104:121–155. doi: 10.1111/j.1600-065x.1988.tb00761.x. [DOI] [PubMed] [Google Scholar]

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