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Experimental Use of Mouse Models of Systemic Lupus Erythematosus

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Autoimmunity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 900))

Abstract

Mouse models of lupus have for many years provided accessible and reliable research systems for the pathogenesis and therapy of systemic autoimmune disease, spanning a spectrum of inbred strains that develop spontaneous disease to experimentally induced, sometimes genetically manipulated animals. Nearly all the models share in common the development of glomerulonephritis and autoantibodies, including antinuclear and DNA specificities, the most common endpoints examined in experimental studies, but exhibit specific differences in the incidence of other end-organ manifestations such as hemolytic anemia, arthritis, dermatitis, and vasculitis. This chapter contrasts the clinical characteristics of these various models, providing an outline for their use and analysis.

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References

  1. Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. New Engl J Med 358:929–939

    PubMed  Google Scholar 

  2. Hahn BH, Singh RR (2007) Animal models of systemic lupus erythematosus. In: Wallace DJ, Hahn BH (eds) Dubois lupus erythematosus. Lippincott Williams & Wilkins, Philadelphia, PA

    Google Scholar 

  3. Davidson A, Aranow C (2009) Lupus nephritis: lessons from murine models. Nat Rev Rheumatol 6:13–20

    PubMed  Google Scholar 

  4. Ghoreishi M, Dutz JP (2009) Murine models of cutaneous involvement in lupus erythematosus. Autoimmun Rev 8:484–487

    PubMed  Google Scholar 

  5. Rottman JB, Willis CR (2010) Mouse models of systemic lupus erythematosus reveal a complex pathogenesis. Vet Pathol 47:664–676

    PubMed  Google Scholar 

  6. Peng SL (2004) Experimental use of murine lupus models. Methods Mol Med 102:227–272

    PubMed  Google Scholar 

  7. Izui S, McConahey PJ, Dixon FJ (1978) Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol 121:2213–2219

    PubMed  Google Scholar 

  8. Andrews BS, Eisenberg RA, Theofilopoulos AN et al (1978) Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148:1198–1215

    PubMed  Google Scholar 

  9. Dixon FJ, Andrews BS, Eisenberg RA et al (1978) Etiology and pathogenesis of a spontaneous lupus-like syndrome in mice. Arthritis Rheum 21:S64–S67

    PubMed  Google Scholar 

  10. Bielschowsky M, Helyer BJ, Howie JB (1959) Spontaneous haemolytic anemia in mice of the NZB/BL strain. Proc Univ Otago Med Sch 37:9

    Google Scholar 

  11. Morel L, Rudofsky UH, Longmate JA et al (1994) Polygenic control of susceptibility to murine systemic lupus erythematosus. Immunity 1:219–229

    PubMed  Google Scholar 

  12. Kaliyaperumal A, Mohan C, Wu W et al (1996) Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. J Exp Med 183:2459–2469

    PubMed  Google Scholar 

  13. Dumont F, Monier JC (1983) Sex-dependent systemic lupus erythematosus-like syndrome in (NZB  ×  SJL)F1 mice. Clin Immunol Immunopathol 29:306–317

    PubMed  Google Scholar 

  14. Vidal S, Gelpi C, Rodriguez-Sanchez JL (1994) (SWR  ×  SJL)F1 mice: a new model of lupus-like disease. J Exp Med 179:1429–1435

    PubMed  Google Scholar 

  15. Watanabe-Fukunaga R, Brannan CI, Copeland NG et al (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317

    PubMed  Google Scholar 

  16. Kelley VE, Roths JB (1985) Interaction of mutant lpr gene with background strain influences renal disease. Clin Immunol Immunopathol 37:220–229

    PubMed  Google Scholar 

  17. Eisenberg RA, Craven SY, Fisher CL et al (1989) The genetics of autoantibody production in MRL/lpr lupus mice. Clin Exp Rheumatol 7:S35–S40

    PubMed  Google Scholar 

  18. Peng SL, Craft J (1999) Lessons from knockout and transgenic lupus-prone mice (chapter 10). In: Kammer GM, Tsokos GC (eds) Lupus: molecular and cellular pathogenesis. Humana Press Inc., Totowa, NJ, pp 152–166

    Google Scholar 

  19. Matsuzawa A, Moriyama T, Kaneko T et al (1990) A new allele of the lpr locus, lpr cg, that complements the gld gene in induction of lymphadenopathy in the mouse. J Exp Med 171:519–531

    PubMed  Google Scholar 

  20. Kimura M, Mohri H, Shimada K et al (1990) Serological and histological characterization of the new mutant strain of lpr mice, CBA/KlJms-lprcg/lprcg. Clin Exp Immunol 79:123–129

    PubMed  Google Scholar 

  21. Adachi M, Suematsu S, Kondo T et al (1995) Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver. Nat Genet 11:294–300

    PubMed  Google Scholar 

  22. Roths JB, Murphy ED, Eicher EM (1984) A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J Exp Med 159:1–20

    PubMed  Google Scholar 

  23. Lynch DH, Watson ML, Alderson MR et al (1994) The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. Immunity 1:131–136

    PubMed  Google Scholar 

  24. Takahashi T, Tanaka M, Brannan CI et al (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76:969–976

    PubMed  Google Scholar 

  25. Pisitkun P, Deane JA, Difilippantonio MJ et al (2006) Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312:1669–1672

    PubMed  Google Scholar 

  26. Subramanian S, Tus K, Li QZ et al (2006) A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc Natl Acad Sci USA 103:9970–9975

    PubMed  Google Scholar 

  27. Izui S, Masuda K, Yoshida H (1984) Acute SLE in F1 hybrids between SB/Le and NZW mice; prominently enhanced formation of gp70 immune complexes by a Y chromosome-associated factor from SB/Le mice. J Immunol 132:701–704

    PubMed  Google Scholar 

  28. Hashimoto Y, Kawamura M, Ichikawa K et al (1992) Anticardiolipin antibodies in NZW  ×  BXSB F1 mice. A model of antiphospholipid syndrome. J Immunol 149:1063–1068

    PubMed  Google Scholar 

  29. Mountz JD, Yang P, Wu Q et al (2005) Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice. Scand J Immunol 61:128–138

    PubMed  Google Scholar 

  30. Kinjoh K, Kyogoku M, Good RA (1993) Genetic selection for crescent formation yields mouse strain with rapidly progressive glomerulonephritis and small vessel vasculitis. Proc Natl Acad Sci USA 90:3413–3417

    PubMed  Google Scholar 

  31. Jethwa HS, Nachman PH, Falk RJ et al (2000) False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: a source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies. Clin Exp Immunol 121:544–550

    PubMed  Google Scholar 

  32. Walker SE, Gray RH, Fulton M et al (1978) Palmerston North mice, a new animal model of systemic lupus erythematosus. J Lab Clin Med 92:932–945

    PubMed  Google Scholar 

  33. Sundberg JP, France M, Boggess D et al (1997) Development and progression of psoriasiform dermatitis and systemic lesions in the flaky skin (fsn) mouse mutant. Pathobiology 65:271–286

    PubMed  Google Scholar 

  34. Pelsue SC, Schweitzer PA, Schweitzer IB et al (1998) Lymphadenopathy, elevated serum IgE levels, autoimmunity, and mast cell accumulation in flaky skin mutant mice. Eur J Immunol 28:1379–1388

    PubMed  Google Scholar 

  35. White RA, McNulty SG, Nsumu NN et al (2005) Positional cloning of the Ttc7 gene required for normal iron homeostasis and mutated in hea and fsn anemia mice. Genomics 85:330–337

    PubMed  Google Scholar 

  36. Satoh M, Reeves WH (1994) Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane. J Exp Med 180:2341–2346

    PubMed  Google Scholar 

  37. Gleichmann H, Gleichmann E, Andre-Schwartz J et al (1972) Chronic allogeneic disease. 3. Genetic requirements for the induction of glomerulonephritis. J Exp Med 135:516–532

    PubMed  Google Scholar 

  38. Van Elven EH, van der Veen FM, Rolink AG et al (1981) Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. V. High titers of IgG autoantibodies to double-stranded DNA. J Immunol 127:2435–2438

    PubMed  Google Scholar 

  39. Chu Y-W, Gress RE (2008) Murine models of chronic graft-versus-host disease: insights and unresolved issues. Biol Blood Marrow Transplant 14:365–378

    PubMed  Google Scholar 

  40. Mendlovic S, Brocke S, Shoenfeld Y et al (1988) Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype. Proc Natl Acad Sci USA 85:2260–2264

    PubMed  Google Scholar 

  41. Blank M, Cohen J, Toder V et al (1991) Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci USA 88:3069–3073

    PubMed  Google Scholar 

  42. Silveira PA, Baxter AG (2001) The NOD mouse as a model of SLE. Autoimmunity 34:53–64

    PubMed  Google Scholar 

  43. Duke Animal Care and Use Program (2011) Guidelines for techniques with rodents. http://vetmed.duhs.duke.edu/guidelines_for_techniques_in_rodents.htm. Accessed 1 Mar 2011

  44. Cattoretti G (2002) Pathology and autopsy of a mouse. http://icg.cpmc.columbia.edu/cattoretti/Protocol/MousePathology/mouseTissue.html. Accessed 1 Mar 2011

  45. Covelli V (1972) Guide to the necropsy of the mouse. http://eulep.pdn.cam.ac.uk/Necropsy_of_the_Mouse/. Accessed 1 Mar 2011

  46. Kurien BT, Scofield RH (1999) Mouse urine collection using clear plastic wrap. Lab Anim 33:83–86

    PubMed  Google Scholar 

  47. Duke Animal Care and Use Program (2011) Guidelines for retro-orbital blood collection. In: Mice. http://vetmed.duhs.duke.edu/guidelines_for_retroorbital_blood_coll_mice.htm. Accessed 1 Mar 2011

  48. Kimura M, Nagase M, Hishida A et al (1987) Intramesangial passage of mononuclear phagocytes in murine lupus glomerulonephritis. Am J Pathol 127:149–156

    PubMed  Google Scholar 

  49. Hoffsten PE, Hill CL, Klahr S (1975) Studies of abluminuria and proteinuria in normal mice and mice with immune complex glomerulonephritis. J Lab Clin Med 86:920–930

    PubMed  Google Scholar 

  50. Ansel JC, Mountz J, Steinberg AD et al (1985) Effects of UV radiation on autoimmune strains of mice: increased mortality and accelerated autoimmunity in BXSB male mice. J Invest Dermatol 85:181–186

    PubMed  Google Scholar 

  51. Davis P, Percy JS (1978) Effect of ultraviolet light on disease characteristics of NZB/W mice. J Rheumatol 5:125–128

    PubMed  Google Scholar 

  52. Isenberg DA, Katz D, Le Page S et al (1991) Independent analysis of the 16/6 idiotype lupus model. A role for an environmental factor? J Immunol 147:4172–4177

    PubMed  Google Scholar 

  53. Maldonado MA, Kakkanaiah V, MacDonald GC et al (1999) The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. J Immunol 162:6322–6330

    PubMed  Google Scholar 

  54. Mizutani A, Shaheen VM, Yoshida H et al (2005) Pristane-induced autoimmunity in germ-free mice. Clin Immunol 114:110–118

    PubMed  Google Scholar 

  55. Hoff J (2000) Methods of blood collection in the mouse. Lab Anim 29:47–53

    Google Scholar 

  56. Hem A, Smith AJ, Solberg P (1998) Saphenous vein puncture for blood sampling of the mouse, rat, hamster, gerbil, guinea pig, ferret and mink. Lab Anim 32:364–368

    PubMed  Google Scholar 

  57. Furner RL, Mellett LB (1975) Mouse restraining chamber for tail-vein injection. Lab Animal Sci 25:648

    Google Scholar 

  58. Durschlag M, Wurbel H, Stauffacher M et al (1996) Repeated blood collection in the laboratory mouse by tail incision–modification of an old technique. Phys Behavior 60:1565–1568

    Google Scholar 

  59. Hijmans W, Radema H, van Es L et al (1969) Cryoglobulins in New Zealand Black mice. Clin Exp Immunol 4:227–239

    PubMed  Google Scholar 

  60. Reininger L, Berney T, Shibata T et al (1990) Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms. Proc Natl Acad Sci USA 87:10038–10042

    PubMed  Google Scholar 

  61. Dammacco F, Sansonno D, Piccoli C et al (2001) The cryoglobulins: an overview. Eur J Clin Invest 31:628–638

    PubMed  Google Scholar 

  62. Peng SL, Craft J (2008) Antinuclear antibodies (chapter 50). In: Firestein GS, Budd RC, Harris ED et al (eds) Kelly’s textbook of rheumatology, 8th edn. Elsevier, Inc., Philadelphia, PA

    Google Scholar 

  63. Shlomchik MJ, Madaio MP, Ni D et al (1994) The role of B cells in lpr/lpr-induced autoimmunity. J Exp Med 180:1295–1306

    PubMed  Google Scholar 

  64. Peng SL, Cappadona J, McNiff JM et al (1998) Pathogenesis of autoimmunity in αβ T cell-deficient lupus-prone mice. Clin Exp Immunol 111:107–116

    PubMed  Google Scholar 

  65. Strasser A, Whittingham S, Vaux DL et al (1991) Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci USA 88:8661–8665

    PubMed  Google Scholar 

  66. Bouillet P, Metcalf D, Huang DC et al (1999) Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735–1738

    PubMed  Google Scholar 

  67. Bouillet P, Purton JF, Godfrey DI et al (2002) BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415:922–926

    PubMed  Google Scholar 

  68. Choi Y, Ramnath VR, Eaton AS et al (1999) Expression in transgenic mice of dominant interfering Fas mutations: a model for human autoimmune lymphoproliferative syndrome. Clin Immunol 93:34–45

    PubMed  Google Scholar 

  69. Murga M, Fernandez-Capetillo O, Field SJ et al (2001) Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity. Immunity 15:959–970

    PubMed  Google Scholar 

  70. Salvador JM, Hollander MC, Nguyen AT et al (2002) Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity 16:499–508

    PubMed  Google Scholar 

  71. Zhang Y, Schlossman SF, Edwards RA et al (2002) Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice. Proc Natl Acad Sci USA 99:878–883

    PubMed  Google Scholar 

  72. Woelfel M, Bixby J, Brehm MA et al (2006) Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity. J Immunol 177:3814–3820

    PubMed  Google Scholar 

  73. Balomenos D, Martin-Caballero J, Garcia MI et al (2000) The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development. Nat Med 6:171–176

    PubMed  Google Scholar 

  74. Lawson BR, Kono DH, Theofilopoulos AN (2002) Deletion of p21 (WAF-1/Cip1) does not induce systemic autoimmunity in female BXSB mice. J Immunol 168:5928–5932

    PubMed  Google Scholar 

  75. Di Cristofano A, Kotsi P, Peng YF et al (1999) Impaired Fas response and autoimmunity in Pten +/− mice. Science 285:2122–2125

    PubMed  Google Scholar 

  76. Suzuki A, Yamaguchi MT, Ohteki T et al (2001) T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity 14:523–534

    PubMed  Google Scholar 

  77. Prodeus AP, Goerg S, Shen LM et al (1998) A critical role for complement in maintenance of self-tolerance. Immunity 9:721–731

    PubMed  Google Scholar 

  78. Scott RS, McMahon EJ, Pop SM et al (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207–211

    PubMed  Google Scholar 

  79. Nash JT, Taylor PR, Botto M et al (2001) Immune complex processing in C1q-deficient mice. Clin Exp Immunol 123:196–202

    PubMed  Google Scholar 

  80. Botto M, Dell’Agnola C, Bygrave AE et al (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19:56–59

    PubMed  Google Scholar 

  81. Napirei M, Karsunky H, Zevnik B et al (2000) Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet 25:177–181

    PubMed  Google Scholar 

  82. Bolland S, Ravetch JV (2000) Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity 13:277–285

    PubMed  Google Scholar 

  83. Boes M, Schmidt T, Linkemann K et al (2000) Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci USA 97:1184–1189

    PubMed  Google Scholar 

  84. A-Gonzalez N, Bensinger SJ, Hong C et al (2009) Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 31:245–258

    PubMed  Google Scholar 

  85. Hanayama R, Tanaka M, Miyasaka K et al (2004) Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304:1147–1150

    PubMed  Google Scholar 

  86. Xue D, Shi H, Smith JD et al (2003) A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proc Natl Acad Sci USA 100:7503–7508

    PubMed  Google Scholar 

  87. Bickerstaff MC, Botto M, Hutchinson WL et al (1999) Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med 5:694–697

    PubMed  Google Scholar 

  88. Lu Q, Lemke G (2001) Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 293:306–311

    PubMed  Google Scholar 

  89. O’Keefe TL, Williams GT, Davies SL et al (1996) Hyperresponsive B cells in CD22-deficient mice. Science 274:798–801

    PubMed  Google Scholar 

  90. Stunz LL, Busch LK, Munroe ME et al (2004) Expression of the cytoplasmic tail of LMP1 in mice induces hyperactivation of B lymphocytes and disordered lymphoid architecture. Immunity 21:255–266

    PubMed  Google Scholar 

  91. Mehling A, Loser K, Varga G et al (2001) Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity. J Exp Med 194:615–628

    PubMed  Google Scholar 

  92. Higuchi T, Aiba Y, Nomura T et al (2002) Cutting edge: ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease. J Immunol 168:9–12

    PubMed  Google Scholar 

  93. Majeti R, Xu Z, Parslow TG et al (2000) An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell 103:1059–1070

    PubMed  Google Scholar 

  94. Li DH, Winslow MM, Cao TM et al (2008) Modulation of peripheral B cell tolerance by CD72 in a murine model. Arthritis Rheum 58:3192–3204

    PubMed  Google Scholar 

  95. Tivol EA, Borriello F, Schweitzer AN et al (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3:541–547

    PubMed  Google Scholar 

  96. Waterhouse P, Penninger JM, Timms E et al (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270:985–988

    PubMed  Google Scholar 

  97. Han B, Moore PA, Wu J et al (2007) Overexpression of human decoy receptor 3 in mice results in a systemic lupus erythematosus-like syndrome. Arthritis Rheum 56:3748–3758

    PubMed  Google Scholar 

  98. Le LQ, Kabarowski JH, Weng Z et al (2001) Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity 14:561–571

    PubMed  Google Scholar 

  99. Yoshinaga SK, Zhang M, Pistillo J et al (2000) Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS. Int Immunol 12:1439–1447

    PubMed  Google Scholar 

  100. Nishimura H, Nose M, Hiai H et al (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:141–151

    PubMed  Google Scholar 

  101. Wilkinson R, Lyons AB, Roberts D et al (2002) Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease. Blood 100:184–193

    PubMed  Google Scholar 

  102. Seshasayee D, Valdez P, Yan M et al (2003) Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity 18:279–288

    PubMed  Google Scholar 

  103. Wen L, Roberts SJ, Viney JL et al (1994) Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in αβ(+) T cells. Nature 369:654–658

    PubMed  Google Scholar 

  104. Wang JH, Avitahl N, Cariappa A et al (1998) Aiolos regulates B cell activation and maturation to effector state. Immunity 9:543–553

    PubMed  Google Scholar 

  105. Shankar M, Nixon JC, Maier S et al (2007) Anti-nuclear antibody production and autoimmunity in transgenic mice that overexpress the transcription factor Bright. J Immunol 178:2996–3006

    PubMed  Google Scholar 

  106. Krawczyk C, Bachmaier K, Sasaki T et al (2000) Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells. Immunity 13:463–473

    PubMed  Google Scholar 

  107. Stohl W, Xu D, Kim KS et al (2005) Humoral autoimmunity in mice overexpressing B cell surface CD19: vital role for MHC class II. Clin Immunol 116:257–264

    PubMed  Google Scholar 

  108. Hsiao HW, Liu WH, Wang CJ et al (2009) Deltex1 is a target of the transcription factor NFAT that promotes T cell anergy. Immunity 31:72–83

    PubMed  Google Scholar 

  109. Zhu B, Symonds AL, Martin JE et al (2008) Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease. J Exp Med 205:2295–2307

    PubMed  Google Scholar 

  110. Shim GJ, Kis LL, Warner M et al (2004) Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor α gene. Proc Natl Acad Sci USA 101:1720–1724

    PubMed  Google Scholar 

  111. Zhang L, Eddy A, Teng YT et al (1995) An immunological renal disease in transgenic mice that overexpress Fli-1, a member of the ets family of transcription factor genes. Mol Cell Biol 15:6961–6970

    PubMed  Google Scholar 

  112. Yu CC, Yen TS, Lowell CA et al (2001) Lupus-like kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn. Curr Biol 11:34–38

    PubMed  Google Scholar 

  113. Li H, Dai M, Zhuang Y (2004) A T cell intrinsic role of Id3 in a mouse model for primary Sjögren’s syndrome. Immunity 21:551–560

    PubMed  Google Scholar 

  114. Hida S, Ogasawara K, Sato K et al (2000) CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-α/β signaling. Immunity 13:643–655

    PubMed  Google Scholar 

  115. Pflegerl P, Vesely P, Hantusch B et al (2009) Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling. Proc Natl Acad Sci USA 106:20423–20428

    PubMed  Google Scholar 

  116. Sommers CL, Park CS, Lee J et al (2002) A LAT mutation that inhibits T cell development yet induces lymphoproliferation. Science 296:2040–2043

    PubMed  Google Scholar 

  117. Hibbs ML, Tarlinton DM, Armes J et al (1995) Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell 83:301–311

    PubMed  Google Scholar 

  118. Nishizumi H, Taniuchi I, Yamanashi Y et al (1995) Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice. Immunity 3:549–560

    PubMed  Google Scholar 

  119. Cornall RJ, Cyster JG, Hibbs ML et al (1998) Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 8:497–508

    PubMed  Google Scholar 

  120. Hurov JB, Stappenbeck TS, Zmasek CM et al (2001) Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase. Mol Cell Biol 21:3206–3219

    PubMed  Google Scholar 

  121. Yoh K, Itoh K, Enomoto A et al (2001) Nrf2-deficient female mice develop lupus-like autoimmune nephritis. Kidney Int 60:1343–1353

    PubMed  Google Scholar 

  122. Miyamoto A, Nakayama K, Imaki H et al (2002) Increased proliferation of B cells and auto-immunity in mice lacking protein kinase C™. Nature 416:865–869

    PubMed  Google Scholar 

  123. Layer K, Lin G, Nencioni A et al (2003) Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity 19:243–255

    PubMed  Google Scholar 

  124. Ishimaru N, Arakaki R, Yoshida S et al (2008) Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sjögren’s syndrome-like autoimmune exocrinopathy. J Exp Med 205:2915–2927

    PubMed  Google Scholar 

  125. Espinosa A, Dardalhon V, Brauner S et al (2009) Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med 206:166–171

    Google Scholar 

  126. Yu D, Tan AH-M, Hu X et al (2007) Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 450:299–303

    PubMed  Google Scholar 

  127. Finetti F, Pellegrini M, Ulivieri C et al (2008) The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity. Blood 111:5017–5027

    PubMed  Google Scholar 

  128. Savino MT, Ortensi B, Ferro M et al (2009) Rai acts as a negative regulator of autoimmunity by inhibiting antigen receptor signaling and lymphocyte activation. J Immunol 182:301–308

    PubMed  Google Scholar 

  129. Shultz LD, Schweitzer PA, Rajan TV et al (1993) Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 73:1445–1454

    PubMed  Google Scholar 

  130. Tsui HW, Siminovitch KA, de Souza L et al (1993) Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet 4:124–129

    PubMed  Google Scholar 

  131. Fujimoto M, Tsutsui H, Xinshou O et al (2004) Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases. Int Immunol 16:303–314

    PubMed  Google Scholar 

  132. Sun H, Lu B, Li RQ et al (2001) Defective T cell activation and autoimmune disorder in Stra13-deficient mice. Nat Immunol 2:1040–1047

    PubMed  Google Scholar 

  133. Drappa J, Kamen LA, Chan E et al (2003) Impaired T cell death and lupus-like autoimmunity in T cell-specific adapter protein-deficient mice. J Exp Med 198:809–821

    PubMed  Google Scholar 

  134. Lech M, Kulkarni OP, Pfeiffer S et al (2008) Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens. J Exp Med 205:1879–1888

    PubMed  Google Scholar 

  135. Mackay F, Woodcock SA, Lawton P et al (1999) Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 190:1697–1710

    PubMed  Google Scholar 

  136. Gross JA, Johnston J, Mudri S et al (2000) TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 404:995–999

    PubMed  Google Scholar 

  137. Khare SD, Sarosi I, Xia XZ et al (2000) Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci USA 97:3370–3375

    PubMed  Google Scholar 

  138. Seery JP (2000) IFN-© transgenic mice: clues to the pathogenesis of systemic lupus erythematosus? Arthritis Res 2:437–440

    PubMed  Google Scholar 

  139. Sadlack B, Lohler J, Schorle H et al (1995) Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur J Immunol 25:3053–3059

    PubMed  Google Scholar 

  140. Willerford DM, Chen J, Ferry JA et al (1995) Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartment. Immunity 3:521–530

    PubMed  Google Scholar 

  141. Suzuki H, Kundig TM, Furlonger C et al (1995) Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor β. Science 268:1472–1476

    PubMed  Google Scholar 

  142. Erb KJ, Ruger B, von Brevern M et al (1997) Constitutive expression of interleukin (IL)-4 in vivo causes autoimmune-type disorders in mice. J Exp Med 185:329–339

    PubMed  Google Scholar 

  143. Vosters JL, Landek-Salgado MA, Yin H et al (2009) Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögren’s syndrome. Arthritis Rheum 60:3633–3641

    PubMed  Google Scholar 

  144. Shen L, Zhang C, Wang T et al (2006) Development of autoimmunity in IL-14α-transgenic mice. J Immunol 177:5676–5686

    PubMed  Google Scholar 

  145. Wang J, Lo JC, Foster A et al (2001) The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT. J Clin Invest 108:1771–1780

    PubMed  Google Scholar 

  146. Carballo E, Lai WS, Blackshear PJ (1998) Feedback inhibition of macrophage tumor necrosis factor-α production by tristetraprolin. Science 281:1001–1005

    PubMed  Google Scholar 

  147. Taylor GA, Carballo E, Lee DM et al (1996) A pathogenetic role for TNF α in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4:445–454

    PubMed  Google Scholar 

  148. Dang H, Geiser AG, Letterio JJ et al (1995) SLE-like autoantibodies and Sjögren’s syndrome-like lymphoproliferation in TGF-β knockout mice. J Immunol 155:3205–3212

    PubMed  Google Scholar 

  149. Yaswen L, Kulkarni AB, Fredrickson T et al (1996) Autoimmune manifestations in the transforming growth factor-β1 knockout mouse. Blood 87:1439–1445

    PubMed  Google Scholar 

  150. Gorelik L, Flavell RA (2000) Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12:171–181

    PubMed  Google Scholar 

  151. Cheng J, Turksen K, Yu QC et al (1992) Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF α transgenic mice. Genes Dev 6:1444–1456

    PubMed  Google Scholar 

  152. Green RS, Stone EL, Tenno M et al (2007) Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis. Immunity 27:308–320

    PubMed  Google Scholar 

  153. Demetriou M, Granovsky M, Quaggin S et al (2001) Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409:733–739

    PubMed  Google Scholar 

  154. Xiao C, Srinivasan L, Calado DP et al (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9:405–414

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Rheumatology Clinical Research Unit, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA

    Stanford L. Peng

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  1. Stanford L. Peng
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Correspondence to Stanford L. Peng .

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  1. College of Medicine, Division of Rheumatology, State University of New York, UMU, East Adams St. 750, Syracuse, 13210, New York, USA

    Andras Perl

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Peng, S.L. (2012). Experimental Use of Mouse Models of Systemic Lupus Erythematosus. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Biology, vol 900. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-720-4_7

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  • DOI: https://doi.org/10.1007/978-1-60761-720-4_7

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  • Publisher Name: Humana Press, Totowa, NJ

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  • Online ISBN: 978-1-60761-720-4

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