Delineation of the Pathogenesis of Systemic Lupus Erythematosus by Using Murine Models

  • Kui Liu
  • Edward K. Wakeland
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 490)


Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the production of autoantibodies to a spectrum of nuclear antigens, and the development of inflammatory Processes potentially affecting multiple organ systems with varied clinical manifestations. Although the etiology of SLE is still unclear, it has been established that genetic factors play an important role in determining disease susceptibility.


Systemic Lupus Erythematosus Lupus Nephritis Epistatic Interaction Congenic Strain Varied Clinical Manifestation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kotzin, BL: Systemic lupus erythematosus. Cell 85:303–306, 1996PubMedCrossRefGoogle Scholar
  2. 2.
    Wakeland, EK, Wandstrat, AE, Liu, K, and Morel, L: Genetic dissection of systemic lupus erythematosus. Curr. Opin. Immunol. 11:701–707, 1999PubMedCrossRefGoogle Scholar
  3. 3.
    Vyse TJ, Kotzin BL: Genetic susceptibility to systemic lupus erythematosus. Ann. Rev. Immunol. 16:261–292,1998CrossRefGoogle Scholar
  4. 4.
    Foster MH: Relevance of systemic lupus erythematosus nephritis animal models to human disease. Semin. Nephrol. 19:12–24,1999Google Scholar
  5. 5.
    Morel L, Rudofsky UH, Longmate JA, Schiffenbauer J, Wakeland EK: Polygenic control of susceptibility to murine systemic lupus erythematosus. Immunity 1:219–229, 1994PubMedCrossRefGoogle Scholar
  6. 6.
    Drake CG, Babcock SK, Palmer E, Kotzin BL: Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice. Proc. Natl. Acad. Sci. U.S.A. 91:4062–4066, 1994PubMedCrossRefGoogle Scholar
  7. 7.
    Kono DH, Burlingame RW, Owens DG, Kuramochi A, Balderas RS, Balomenos D, Theofilopoulos AN: Lupus susceptibility loci in New Zealand mice. Proc. Natl. Acad. Sci. U. S. A. 91:10168–10172,1994PubMedCrossRefGoogle Scholar
  8. 8.
    Hogarth MB, Slingsby JH, Allen PJ, Thompson EM, Chandler P, Davies KA, Simpson E, Morley BJ, Walport MJ: Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. J. Immunol. 161:2753–2761, 1998PubMedGoogle Scholar
  9. 9.
    Watson ML, Rao JK, Gilkeson GS, Ruiz P, Eicher EM, Pisetsky DS, Matsuzawa A, Rochelle JM, Seldin MF: Genetic analysis of MRL-Ipr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci. J. Exp. Med. 176:1645–1656, 1992PubMedCrossRefGoogle Scholar
  10. 10.
    Vidal S, Kono DH, Theofilopoulos AN: Loci predisposing to autoimmunity in MRLFasIF and C57BL/6-FasiP` mice. J. Clin. Invest.101:696–702, 1998PubMedCrossRefGoogle Scholar
  11. 11.
    Morel L, Mohan C, Yu Y, Schiffenbauer J, Rudofsky UH, Tian N, Longmate JA, Wakeland EK: Multiplex inheritance of component phenotypes in a murine model of lupus. Mamm, Genome, 10:176–181, 1999Google Scholar
  12. 12.
    Morel L, Yu Y, Blenman KR, Caldwell RA, Wakeland EK: Production of congenie mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain. Mamm. Genome 7:335–339, 1996Google Scholar
  13. 13.
    Mohan C, Morel L, Yang P, Watanabe H, Croker B, Gilkeson G, Wakeland EK: Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies. J. Clin. Invest. 103:1685–1695, 1999PubMedCrossRefGoogle Scholar
  14. 14.
    Morel L, Croker BP, Blenman KR, Mohan C, Huang G, Gilkeson G, Wakeland EK: Genetic reconstitution of systemic lupus erythematosus immunopathology with poly-congenie murine strains. Proc. Natl. Acad. Sci. U.S.A. 97:6670–6675, 2000PubMedCrossRefGoogle Scholar
  15. 15.
    Botto M, Dell’Agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, Loos M, Pandolfi PP, Walport MJ: Homozygous C 1 q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19:56–59, 1998Google Scholar
  16. 16.
    Bickerstaff MC, Botto M, Hutchinson WL, Herbert J, Tennent GA, Bybee A, Mitchell DA, Cook HT, Butler PJ, Walport MJ, Pepys MB: Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat. Med. 5:694–697, 1999Google Scholar
  17. 17.
    Balomenos D, Martin-Caballero J, Garcia MI, Prieto I, Flores JM, Serrano M, Martinez AC: The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development. Nat. Med. 6:171–176, 2000PubMedCrossRefGoogle Scholar
  18. 18.
    Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata, S: Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317, 1992PubMedCrossRefGoogle Scholar
  19. 19.
    Roths JB, Murphy ED, Eicher EM: A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J. Exp. Med. 159:1–20,1984PubMedCrossRefGoogle Scholar
  20. 20.
    Cornall RJ, Cyster JG, Hibbs ML, Dunn AR, Otibopy KL, Clark EA, Goodnow CC: Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 8:497–508, 1998PubMedCrossRefGoogle Scholar
  21. 21.
    Clynes R, Dumitru C, Ravetch JV: Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science 279:1052–1054, 1998PubMedCrossRefGoogle Scholar
  22. 22.
    Mohan C, Yu Y, Morel L, Yang P, Wakeland EK: Genetic dissection of SLE pathogenesis:S1e3on murine chromosome 7 impacts T cell activation, differentiation, and cell death. J. Immunol. 162:6492–6502, 1999PubMedGoogle Scholar
  23. 23.
    Lajaunias F, Ibnou-Zekri N, Fossati-Jimack L, Chicheportiche Y, Parkhouse RM, Mary C, Reininger L, Brighouse G, Izui S: Polymorphisms in the Cd22 gene of inbred mouse strains. Immunogenetics 49:991–995, 1999PubMedCrossRefGoogle Scholar
  24. 24.
    Gorelik L, Flavel RA: Abrogation of TGF signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12:171–181, 2000PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Kui Liu
    • 1
  • Edward K. Wakeland
    • 1
  1. 1.Center for ImmunologyThe University of Texas Southwestern Medical Center at DallasDallasUSA

Personalised recommendations