Insights into the genetic basis and immunopathogenesis of systemic lupus erythematosus from the study of mouse models

Seminars in Immunology

Volumn 21, Issue 6, 2009, Pages 372-382

  Cheung, Yui Ho ^a,b   Loh, Christina ^a,b   Pau, Evelyn ^a,b   Kim, Julie ^a,b   Wither, Joan ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b TORONTO WESTERN HOSPITAL   (Canada)

Author keywords

Congenic mice; Genetics; Knock out mice; Pathogenesis; Systemic lupus erythematosus

Indexed keywords

APOPTOSIS; AUTOIMMUNITY; CELL SURVIVAL; CHROMOSOME 1; CHROMOSOME 13; CHROMOSOME 4; CHROMOSOME 7; CONGENIC STRAIN; GENE DELETION; GENETIC ASSOCIATION; GENETIC MANIPULATION; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; HUMAN; HUMAN GENETICS; IMMUNOGENETICS; IMMUNOPATHOLOGY; KNOCKOUT MOUSE; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; TRANSGENIC MOUSE; Y CHROMOSOME;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MICE; MICE, CONGENIC; MICE, TRANSGENIC;

EID: 70749147691     PISSN: 10445323     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.smim.2009.10.005     Document Type: Review

References (174)

1. Kotzin B.L. Systemic lupus erythematosus. Cell 85 (1996) 303-306
2. Hahn B.H. Antibodies to DNA. N Engl J Med 338 (1998) 1359-1368
3. Dubois E.L. Dubois' lupus erythematosus. 2nd revised ed. (1976), USA Press, Los Angeles
4. Boumpas D.T., Fessler B.J., Austin III H.A., Balow J.E., Klippel J.H., and Lockshin M.D. Systemic lupus erythematosus: emerging concepts. Part 2. Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis. Ann Intern Med 123 (1995) 42-53
5. Boumpas D.T., Austin III H.A., Fessler B.J., Balow J.E., Klippel J.H., and Lockshin M.D. Systemic lupus erythematosus: emerging concepts. Part 1. Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med 122 (1995) 940-950
6. Mills J.A. Systemic lupus erythematosus. N Engl J Med 330 (1994) 1871-1879
7. Hochberg M.C. The application of genetic epidemiology to systemic lupus erythematosus. J Rheumatol 14 (1987) 867-869
8. Deapen D., Escalante A., Weinrib L., Horwitz D., Bachman B., Roy-Burman P., et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 35 (1992) 311-318
9. Block S.R., Winfield J.B., Lockshin M.D., D'Angelo W.A., and Christian C.L. Studies of twins with systemic lupus erythematosus. A review of the literature and presentation of 12 additional sets. Am J Med 59 (1975) 533-552
10. Moser K.L., Kelly J.A., Lessard C.J., and Harley J.B. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun 10 (2009) 373-379
11. Wakeland E.K., Liu K., Graham R.R., and Behrens T.W. Delineating the genetic basis of systemic lupus erythematosus. Immunity 15 (2001) 397-408
12. Gaipl U.S., Voll R.E., Sheriff A., Franz S., Kalden J.R., and Herrmann M. Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun Rev 4 (2005) 189-194
13. Kaplan M.J. Apoptosis in systemic lupus erythematosus. Clin Immunol 112 (2004) 210-218
14. Munoz L.E., Gaipl U.S., Franz S., Sheriff A., Voll R.E., Kalden J.R., et al. SLE-a disease of clearance deficiency?. Rheumatology (Oxford) 44 (2005) 1101-1107
15. Gaipl U.S., Beyer T.D., Baumann I., Voll R.E., Stach C.M., Heyder P., et al. Exposure of anionic phospholipids serves as anti-inflammatory and immunosuppressive signal-implications for antiphospholipid syndrome and systemic lupus erythematosus. Immunobiology 207 (2003) 73-81
16. Voll R.E., Herrmann M., Roth E.A., Stach C., Kalden J.R., and Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature 390 (1997) 350-351
17. Fadok V.A., Bratton D.L., Konowal A., Freed P.W., Westcott J.Y., and Henson P.M. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101 (1998) 890-898
18. Taylor P.R., Carugati A., Fadok V.A., Cook H.T., Andrews M., Carroll M.C., et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192 (2000) 359-366
19. Cohen P.L., Caricchio R., Abraham V., Camenisch T.D., Jennette J.C., Roubey R.A., et al. Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J Exp Med 196 (2002) 135-140
20. Gonzalez N., Bensinger S.J., Hong C., Beceiro S., Bradley M.N., Zelcer N., et al. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 31 (2009) 245-258
21. Hanayama R., Tanaka M., Miyasaka K., Aozasa K., Koike M., Uchiyama Y., et al. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304 (2004) 1147-1150
22. Munoz L.E., Janko C., Grossmayer G.E., Frey B., Voll R.E., Kern P., et al. Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus. Arthritis Rheum 60 (2009) 1733-1742
23. Napirei M., Karsunky H., Zevnik B., Stephan H., Mannherz H.G., and Moroy T. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet 25 (2000) 177-181
24. Bickerstaff M.C., Botto M., Hutchinson W.L., Herbert J., Tennent G.A., Bybee A., et al. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med 5 (1999) 694-697
25. Xue D., Shi H., Smith J.D., Chen X., Noe D.A., Cedervall T., et al. A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proc Natl Acad Sci USA 100 (2003) 7503-7508
26. Christensen S.R., and Shlomchik M.J. Regulation of lupus-related autoantibody production and clinical disease by Toll-like receptors. Semin Immunol 19 (2007) 11-23
27. Marshak-Rothstein A. Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 6 (2006) 823-835
28. Baccala R., Hoebe K., Kono D.H., Beutler B., and Theofilopoulos A.N. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nat Med 13 (2007) 543-551
29. Santiago-Raber M.L., Baccala R., Haraldsson K.M., Choubey D., Stewart T.A., Kono D.H., et al. Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. J Exp Med 197 (2003) 777-788
30. Deane J.A., Pisitkun P., Barrett R.S., Feigenbaum L., Town T., Ward J.M., et al. Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity 27 (2007) 801-810
31. Lech M., Kulkarni O.P., Pfeiffer S., Savarese E., Krug A., Garlanda C., et al. Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens. J Exp Med 205 (2008) 1879-1888
32. O'Keefe T.L., Williams G.T., Batista F.D., and Neuberger M.S. Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies. J Exp Med 189 (1999) 1307-1313
33. Pani G., Siminovitch K.A., and Paige C.J. The motheaten mutation rescues B cell signaling and development in CD45-deficient mice. J Exp Med 186 (1997) 581-588
34. Hibbs M.L., Tarlinton D.M., Armes J., Grail D., Hodgson G., Maglitto R., et al. Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell 83 (1995) 301-311
35. Cornall R.J., Cyster J.G., Hibbs M.L., Dunn A.R., Otipoby K.L., Clark E.A., et al. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 8 (1998) 497-508
36. Tedder T.F., Inaoki M., and Sato S. The CD19-CD21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity 6 (1997) 107-118
37. Le L.Q., Kabarowski J.H., Weng Z., Satterthwaite A.B., Harvill E.T., Jensen E.R., et al. Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity 14 (2001) 561-571
38. Salvador J.M., Hollander M.C., Nguyen A.T., Kopp J.B., Barisoni L., Moore J.K., et al. Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity 16 (2002) 499-508
39. Linterman M.A., Rigby R.J., Wong R.K., Yu D., Brink R., Cannons J.L., et al. Follicular helper T cells are required for systemic autoimmunity. J Exp Med 206 (2009) 561-576
40. Espinosa A., Dardalhon V., Brauner S., Ambrosi A., Higgs R., Quintana F.J., et al. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med 206 (2009) 1661-1671
41. Majeti R., Xu Z., Parslow T.G., Olson J.L., Daikh D.I., Killeen N., et al. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell 103 (2000) 1059-1070
42. Savino M.T., Ortensi B., Ferro M., Ulivieri C., Fanigliulo D., Paccagnini E., et al. Rai acts as a negative regulator of autoimmunity by inhibiting antigen receptor signaling and lymphocyte activation. J Immunol 182 (2009) 301-308
43. Finetti F., Pellegrini M., Ulivieri C., Savino M.T., Paccagnini E., Ginanneschi C., et al. The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity. Blood 111 (2008) 5017-5027
44. Nishimura H., Nose M., Hiai H., Minato N., and Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11 (1999) 141-151
45. Okazaki T., and Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol 27 (2006) 195-201
46. Takahashi T., Tanaka M., Brannan C.I., Jenkins N.A., Copeland N.G., Suda T., et al. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76 (1994) 969-976
47. Nagata S., and Suda T. Fas and Fas ligand: lpr and gld mutations. Immunol Today 16 (1995) 39-43
48. Bouillet P., Metcalf D., Huang D.C., Tarlinton D.M., Kay T.W., Kontgen F., et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286 (1999) 1735-1738
49. Strasser A., Whittingham S., Vaux D.L., Bath M.L., Adams J.M., Cory S., et al. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci USA 88 (1991) 8661-8665
50. Mackay F., Woodcock S.A., Lawton P., Ambrose C., Baetscher M., Schneider P., et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 190 (1999) 1697-1710
51. Di C.A., Kotsi P., Peng Y.F., Cordon-Cardo C., Elkon K.B., and Pandolfi P.P. Impaired Fas response and autoimmunity in Pten+/- mice. Science 285 (1999) 2122-2125
52. Rathmell J.C., and Goodnow C.C. Effects of the lpr mutation on elimination and inactivation of self-reactive B cells. J Immunol 153 (1994) 2831-2842
53. Oliver P.M., Vass T., Kappler J., and Marrack P. Loss of the proapoptotic protein, Bim, breaks B cell anergy. J Exp Med 203 (2006) 731-741
54. Thien M., Phan T.G., Gardam S., Amesbury M., Basten A., Mackay F., et al. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity 20 (2004) 785-798
55. Hao Z., Duncan G.S., Seagal J., Su Y.W., Hong C., Haight J., et al. Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis. Immunity 29 (2008) 615-627
56. Fischer S.F., Bouillet P., O'Donnell K., Light A., Tarlinton D.M., and Strasser A. Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells. Blood 110 (2007) 3978-3984
57. Smith K.G., Light A., O'Reilly L.A., Ang S.M., Strasser A., and Tarlinton D. Bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody-forming cells. J Exp Med 191 (2000) 475-484
58. Stohl W., Jacob N., Quinn III W.J., Cancro M.P., Gao H., Putterman C., et al. Global T cell dysregulation in non-autoimmune-prone mice promotes rapid development of BAFF-independent, systemic lupus erythematosus-like autoimmunity. J Immunol 181 (2008) 833-841
59. Wenderfer S.E., Wang H., Ke B., Wetsel R.A., and Braun M.C. C3a receptor deficiency accelerates the onset of renal injury in the MRL/lpr mouse. Mol Immunol 46 (2009) 1397-1404
60. Wenderfer S.E., Ke B., Hollmann T.J., Wetsel R.A., Lan H.Y., and Braun M.C. C5a receptor deficiency attenuates T cell function and renal disease in MRLlpr mice. J Am Soc Nephrol 16 (2005) 3572-3582
61. Lenda D.M., Stanley E.R., and Kelley V.R. Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Fas(lpr) mice. J Immunol 173 (2004) 4744-4754
62. Hoi A.Y., Hickey M.J., Hall P., Yamana J., O'Sullivan K.M., Santos L.L., et al. Macrophage migration inhibitory factor deficiency attenuates macrophage recruitment, glomerulonephritis, and lethality in MRL/lpr mice. J Immunol 177 (2006) 5687-5696
63. Tesch G.H., Maifert S., Schwarting A., Rollins B.J., and Kelley V.R. Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice. J Exp Med 190 (1999) 1813-1824
64. Perez de L.G., Maier H., Franz T.J., Escribese M., Chilla S., Segerer S., et al. Chemokine receptor Ccr2 deficiency reduces renal disease and prolongs survival in MRL/lpr lupus-prone mice. J Am Soc Nephrol 16 (2005) 3592-3601
65. He X., Schoeb T.R., Panoskaltsis-Mortari A., Zinn K.R., Kesterson R.A., Zhang J., et al. Deficiency of P-selectin or P-selectin glycoprotein ligand-1 leads to accelerated development of glomerulonephritis and increased expression of CC chemokine ligand 2 in lupus-prone mice. J Immunol 177 (2006) 8748-8756
66. Theofilopoulos A.N., and Dixon F.J. Murine models of systemic lupus erythematosus. Adv Immunol 37 (1985) 269-390
67. Morel L., Yu Y., Blenman K.R., Caldwell R.A., and Wakeland E.K. Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain. Mamm Genome 7 (1996) 335-339
68. Morel L., Mohan C., Yu Y., Croker B.P., Tian N., Deng A., et al. Functional dissection of systemic lupus erythematosus using congenic mouse strains. J Immunol 158 (1997) 6019-6028
69. Mohan C., Morel L., Yang P., Watanabe H., Croker B., Gilkeson G., et al. Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies. J Clin Invest 103 (1999) 1685-1695
70. Morel L., Croker B.P., Blenman K.R., Mohan C., Huang G., Gilkeson G., et al. Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains. Proc Natl Acad Sci USA 97 (2000) 6670-6675
71. Mohan C., Alas E., Morel L., Yang P., and Wakeland E.K. Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. J Clin Invest 101 (1998) 1362-1372
72. Mohan C., Morel L., Yang P., and Wakeland E.K. Genetic dissection of systemic lupus erythematosus pathogenesis: Sle2 on murine chromosome 4 leads to B cell hyperactivity. J Immunol 159 (1997) 454-465
73. Morel L., Blenman K.R., Croker B.P., and Wakeland E.K. The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes. Proc Natl Acad Sci USA 98 (2001) 1787-1792
74. Morel L., Tian X.H., Croker B.P., and Wakeland E.K. Epistatic modifiers of autoimmunity in a murine model of lupus nephritis. Immunity 11 (1999) 131-139
75. Bolland S., Yim Y.S., Tus K., Wakeland E.K., and Ravetch J.V. Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(-/-) mice. J Exp Med 195 (2002) 1167-1174
76. Murphy E.D., and Roths J.B. A Y chromosome associated factor in strain BXSB producing accelerated autoimmunity and lymphoproliferation. Arthritis Rheum 22 (1979) 1188-1194
77. Izui S., Higaki M., Morrow D., and Merino R. The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus-like syndrome in (NZW × C57BL/6)F1 male mice, but not in C57BL/6 male mice. Eur J Immunol 18 (1988) 911-915
78. Pisitkun P., Deane J.A., Difilippantonio M.J., Tarasenko T., Satterthwaite A.B., and Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312 (2006) 1669-1672
79. Subramanian S., Tus K., Li Q.Z., Wang A., Tian X.H., Zhou J., et al. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc Natl Acad Sci USA 103 (2006) 9970-9975
80. Santiago-Raber M.L., Kikuchi S., Borel P., Uematsu S., Akira S., Kotzin B.L., et al. Evidence for genes in addition to Tlr7 in the Yaa translocation linked with acceleration of systemic lupus erythematosus. J Immunol 181 (2008) 1556-1562
81. Fairhurst A.M., Hwang S.H., Wang A., Tian X.H., Boudreaux C., Zhou X.J., et al. Yaa autoimmune phenotypes are conferred by overexpression of TLR7. Eur J Immunol 38 (2008) 1971-1978
82. Ichii O., Konno A., Sasaki N., Endoh D., Hashimoto Y., and Kon Y. Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ. Histol Histopathol 23 (2008) 411-422
83. Hogarth M.B., Slingsby J.H., Allen P.J., Thompson E.M., Chandler P., Davies K.A., et al. Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. J Immunol 161 (1998) 2753-2761
84. Vyse T.J., Rozzo S.J., Drake C.G., Izui S., and Kotzin B.L. Control of multiple autoantibodies linked with a lupus nephritis susceptibility locus in New Zealand black mice. J Immunol 158 (1997) 5566-5574
85. Morel L., Rudofsky U.H., Longmate J.A., Schiffenbauer J., and Wakeland E.K. Polygenic control of susceptibility to murine systemic lupus erythematosus. Immunity 1 (1994) 219-229
86. Rozzo S.J., Allard J.D., Choubey D., Vyse T.J., Izui S., Peltz G., et al. Evidence for an interferon-inducible gene, Ifi202, in the susceptibility to systemic lupus. Immunity 15 (2001) 435-443
87. Wither J.E., Lajoie G., Heinrichs S., Cai Y.C., Chang N., Ciofani A., et al. Functional dissection of lupus susceptibility loci on the New Zealand black mouse chromosome 1: evidence for independent genetic loci affecting T and B cell activation. J Immunol 171 (2003) 1697-1706
88. Sobel E.S., Mohan C., Morel L., Schiffenbauer J., and Wakeland E.K. Genetic dissection of SLE pathogenesis: adoptive transfer of Sle1 mediates the loss of tolerance by bone marrow-derived B cells. J Immunol 162 (1999) 2415-2421
89. Kumar K.R., Li L., Yan M., Bhaskarabhatla M., Mobley A.B., Nguyen C., et al. Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science 312 (2006) 1665-1669
90. Vuyyuru R., Mohan C., Manser T., and Rahman Z.S. The lupus susceptibility locus sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints. J Immunol 183 (2009) 5716-5727
91. Wandstrat A.E., Nguyen C., Limaye N., Chan A.Y., Subramanian S., Tian X.H., et al. Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus. Immunity 21 (2004) 769-780
92. Bottino C., Falco M., Parolini S., Marcenaro E., Augugliaro R., Sivori S., et al. NTB-A [correction of GNTB-A], a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked lymphoproliferative disease. J Exp Med 194 (2001) 235-246
93. Peck S.R., and Ruley H.E. Ly108: a new member of the mouse CD2 family of cell surface proteins. Immunogenetics 52 (2000) 63-72
94. Zhong M.C., and Veillette A. Control of T lymphocyte signaling by Ly108, a signaling lymphocytic activation molecule family receptor implicated in autoimmunity. J Biol Chem 283 (2008) 19255-19264
95. Xie C., Patel R., Wu T., Zhu J., Henry T., Bhaskarabhatla M., et al. PI3K/AKT/mTOR hypersignaling in autoimmune lymphoproliferative disease engendered by the epistatic interplay of Sle1b and FASlpr. Int Immunol 19 (2007) 509-522
96. Boackle S.A., Holers V.M., Chen X., Szakonyi G., Karp D.R., Wakeland E.K., et al. Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15 (2001) 775-785
97. Chen Y., Perry D., Boackle S.A., Sobel E.S., Molina H., Croker B.P., et al. Several genes contribute to the production of autoreactive B and T cells in the murine lupus susceptibility locus Sle1c. J Immunol 175 (2005) 1080-1089
98. Cheung Y.H., Chang N.H., Cai Y.C., Bonventi G., MacLeod R., and Wither J.E. Functional interplay between intrinsic B and T cell defects leads to amplification of autoimmune disease in New Zealand black chromosome 1 congenic mice. J Immunol 175 (2005) 8154-8164
99. Jiang Y., Hirose S., Sanokawa-Akakura R., Abe M., Mi X., Li N., et al. Genetically determined aberrant down-regulation of FcgammaRIIB1 in germinal center B cells associated with hyper-IgG and IgG autoantibodies in murine systemic lupus erythematosus. Int Immunol 11 (1999) 1685-1691
100. Xiu Y., Nakamura K., Abe M., Li N., Wen X.S., Jiang Y., et al. Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses. J Immunol 169 (2002) 4340-4346
101. Fukuyama H., Nimmerjahn F., and Ravetch J.V. The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells. Nat Immunol 6 (2005) 99-106
102. Rahman Z.S., Alabyev B., and Manser T. FcgammaRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity. J Immunol 178 (2007) 897-907
103. Rahman Z.S., Niu H., Perry D., Wakeland E., Manser T., and Morel L. Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production. Genes Immun 8 (2007) 604-612
104. Wither J.E., Paterson A.D., and Vukusic B. Genetic dissection of B cell traits in New Zealand black mice. The expanded population of B cells expressing up-regulated costimulatory molecules shows linkage to Nba2. Eur J Immunol 30 (2000) 356-365
105. Gohlke P.R., Williams J.C., Vilen B.J., Dillon S.R., Tisch R., and Matsushima G.K. The receptor tyrosine kinase MerTK regulates dendritic cell production of BAFF. Autoimmunity 42 (2009) 183-197
106. Yamauchi M., Hashimoto M., Ichiyama K., Yoshida R., Hanada T., Muta T., et al. Ifi202, an IFN-inducible candidate gene for lupus susceptibility in NZB/W F1 mice, is a positive regulator for NF-kappaB activation in dendritic cells. Int Immunol 19 (2007) 935-942
107. Ichii O., Konno A., Sasaki N., Endoh D., Hashimoto Y., and Kon Y. Altered balance of inhibitory and active Fc gamma receptors in murine autoimmune glomerulonephritis. Kidney Int 74 (2008) 339-347
108. Haywood M.E., Rogers N.J., Rose S.J., Boyle J., McDermott A., Rankin J.M., et al. Dissection of BXSB lupus phenotype using mice congenic for chromosome 1 demonstrates that separate intervals direct different aspects of disease. J Immunol 173 (2004) 4277-4285
109. Jiang Y., Hirose S., Abe M., Sanokawa-Akakura R., Ohtsuji M., Mi X., et al. Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility. Immunogenetics 51 (2000) 429-435
110. Pritchard N.R., Cutler A.J., Uribe S., Chadban S.J., Morley B.J., and Smith K.G. Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcgammaRII. Curr Biol 10 (2000) 227-230
111. Lin Q., Xiu Y., Jiang Y., Tsurui H., Nakamura K., Kodera S., et al. Genetic dissection of the effects of stimulatory and inhibitory IgG Fc receptors on murine lupus. J Immunol 177 (2006) 1646-1654
112. Jiang Y., Hirose S., Hamano Y., Kodera S., Tsurui H., Abe M., et al. Mapping of a gene for the increased susceptibility of B1 cells to Mott cell formation in murine autoimmune disease. J Immunol 158 (1997) 992-997
113. Hirose S., Sekigawa I., Ozaki S., Sato H., and Shirai T. Genetic regulation of hypergammaglobulinaemia and the correlation to autoimmune traits in (NZB × NZW) F1 hybrid. Clin Exp Immunol 58 (1984) 694-702
114. Ochiai K., Ozaki S., Tanino A., Watanabe S., Ueno T., Mitsui K., et al. Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand black mice. Int Immunol 12 (2000) 1-8
115. Rigby R.J., Rozzo S.J., Boyle J.J., Lewis M., Kotzin B.L., and Vyse T.J. New loci from New Zealand Black and New Zealand White mice on chromosomes 4 and 12 contribute to lupus-like disease in the context of BALB/c. J Immunol 172 (2004) 4609-4617
116. Waters S.T., Fu S.M., Gaskin F., Deshmukh U.S., Sung S.S., Kannapell C.C., et al. NZM2328: a new mouse model of systemic lupus erythematosus with unique genetic susceptibility loci. Clin Immunol 100 (2001) 372-383
117. Santiago-Raber M.L., Laporte C., Reininger L., and Izui S. Genetic basis of murine lupus. Autoimmun Rev 3 (2004) 33-39
118. Berland R., and Wortis H.H. Origins and functions of B-1 cells with notes on the role of CD5. Annu Rev Immunol 20 (2002) 253-300
119. Xu Z., Duan B., Croker B.P., Wakeland E.K., and Morel L. Genetic dissection of the murine lupus susceptibility locus Sle2: contributions to increased peritoneal B-1a cells and lupus nephritis map to different loci. J Immunol 175 (2005) 936-943
120. Liu Y., Li L., Kumar K.R., Xie C., Lightfoot S., Zhou X.J., et al. Lupus susceptibility genes may breach tolerance to DNA by impairing receptor editing of nuclear antigen-reactive B cells. J Immunol 179 (2007) 1340-1352
121. Loh C., Cai Y.C., Bonventi G., Lajoie G., MacLeod R., and Wither J.E. Dissociation of the genetic loci leading to b1a and NKT cell expansions from autoantibody production and renal disease in b6 mice with an introgressed New Zealand black chromosome 4 interval. J Immunol 178 (2007) 1608-1617
122. Xu Z., Butfiloski E.J., Sobel E.S., and Morel L. Mechanisms of peritoneal B-1a cells accumulation induced by murine lupus susceptibility locus Sle2. J Immunol 173 (2004) 6050-6058
123. Haraldsson M.K., la Paz N.G., Kuan J.G., Gilkeson G.S., Theofilopoulos A.N., and Kono D.H. Autoimmune alterations induced by the New Zealand Black Lbw2 locus in BWF1 mice. J Immunol 174 (2005) 5065-5073
124. Waters S.T., McDuffie M., Bagavant H., Deshmukh U.S., Gaskin F., Jiang C., et al. Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens is not required for the pathogenesis of lupus glomerulonephritis. J Exp Med 199 (2004) 255-264
125. Santiago-Raber M.L., Haraldsson M.K., Theofilopoulos A.N., and Kono D.H. Characterization of reciprocal Lmb1-4 interval MRL-Faslpr and C57BL/6-Faslpr congenic mice reveals significant effects from Lmb3. J Immunol 178 (2007) 8195-8202
126. Xie S., Chang S.H., Sedrak P., Kaliyaperumal A., Datta S.K., and Mohan C. Dominant NZB contributions to lupus in the (SWR × NZB)F1 model. Genes Immun 3 Suppl 1 (2002) S13-S20
127. Vidal S., Kono D.H., and Theofilopoulos A.N. Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice. J Clin Invest 101 (1998) 696-702
128. Mohan C., Yu Y., Morel L., Yang P., and Wakeland E.K. Genetic dissection of Sle pathogenesis: Sle3 on murine chromosome 7 impacts T cell activation, differentiation, and cell death. J Immunol 162 (1999) 6492-6502
129. Wakui M., Morel L., Butfiloski E.J., Kim C., and Sobel E.S. Genetic dissection of systemic lupus erythematosus pathogenesis: partial functional complementation between Sle1 and Sle3/5 demonstrates requirement for intracellular coexpression for full phenotypic expression of lupus. J Immunol 175 (2005) 1337-1345
130. Sobel E.S., Morel L., Baert R., Mohan C., Schiffenbauer J., and Wakeland E.K. Genetic dissection of systemic lupus erythematosus pathogenesis: evidence for functional expression of Sle3/5 by non-T cells. J Immunol 169 (2002) 4025-4032
131. Liu K., Li Q.Z., Yu Y., Liang C., Subramanian S., Zeng Z., et al. Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis. Genes Immun 8 (2007) 634-645
132. Zhu J., Liu X., Xie C., Yan M., Yu Y., Sobel E.S., et al. T cell hyperactivity in lupus as a consequence of hyperstimulatory antigen-presenting cells. J Clin Invest 115 (2005) 1869-1878
133. Jacob C.O., Zhu J., Armstrong D.L., Yan M., Han J., Zhou X.J., et al. Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus. Proc Natl Acad Sci USA 106 (2009) 6256-6261
134. Liu K., Li Q.Z., gado-Vega A.M., Abelson A.K., Sanchez E., Kelly J.A., et al. Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans. J Clin Invest 119 (2009) 911-923
135. Li Q.Z., Zhou J., Yang R., Yan M., Ye Q., Liu K., et al. The lupus-susceptibility gene kallikrein downmodulates antibody-mediated glomerulonephritis. Genes Immun 10 (2009) 503-508
136. Haraldsson M.K., Louis-Dit-Sully C.A., Lawson B.R., Sternik G., Santiago-Raber M.L., Gascoigne N.R., et al. The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation. Immunity 28 (2008) 40-51
137. Humphries C.L., Balcer H.I., D'Agostino J.L., Winsor B., Drubin D.G., Barnes G., et al. Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin. J Cell Biol 159 (2002) 993-1004
138. Foger N., Rangell L., Danilenko D.M., and Chan A.C. Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis. Science 313 (2006) 839-842
139. Mueller P., Massner J., Jayachandran R., Combaluzier B., Albrecht I., Gatfield J., et al. Regulation of T cell survival through coronin-1-mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering. Nat Immunol 9 (2008) 424-431
140. Vyse T.J., and Kotzin B.L. Genetic basis of systemic lupus erythematosus. Curr Opin Immunol 8 (1996) 843-851
141. Santiago M.L., Mary C., Parzy D., Jacquet C., Montagutelli X., Parkhouse R.M., et al. Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW × C57BL/6)F1 mice. Eur J Immunol 28 (1998) 4257-4267
142. Haywood M.E., Vyse T.J., McDermott A., Thompson E.M., Ida A., Walport M.J., et al. Autoantigen glycoprotein 70 expression is regulated by a single locus, which acts as a checkpoint for pathogenic anti-glycoprotein 70 autoantibody production and hence for the corresponding development of severe nephritis, in lupus-prone PXSB mice. J Immunol 167 (2001) 1728-1733
143. Wither J.E., Loh C., Lajoie G., Heinrichs S., Cai Y.C., Bonventi G., et al. Colocalization of expansion of the splenic marginal zone population with abnormal B cell activation and autoantibody production in B6 mice with an introgressed New Zealand Black chromosome 13 interval. J Immunol 175 (2005) 4309-4319
144. Izui S., McConahey P.J., Theofilopoulos A.N., and Dixon F.J. Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus. J Exp Med 149 (1979) 1099-1116
145. Izui S., McConahey P.J., Clark J.P., Hang L.M., Hara I., and Dixon F.J. Retroviral gp70 immune complexes in NZB × NZW F2 mice with murine lupus nephritis. J Exp Med 154 (1981) 517-528
146. Tabata N., Miyazawa M., Fujisawa R., Takei Y.A., Abe H., and Hashimoto K. Establishment of monoclonal anti-retroviral gp70 autoantibodies from MRL/lpr lupus mice and induction of glomerular gp70 deposition and pathology by transfer into non-autoimmune mice. J Virol 74 (2000) 4116-4126
147. Laporte C., Ballester B., Mary C., Izui S., and Reininger L. The Sgp3 locus on mouse chromosome 13 regulates nephritogenic gp70 autoantigen expression and predisposes to autoimmunity. J Immunol 171 (2003) 3872-3877
148. Kikuchi S., Fossati-Jimack L., Moll T., Amano H., Amano E., Ida A., et al. Differential role of three major New Zealand Black-derived loci linked with Yaa-induced murine lupus nephritis. J Immunol 174 (2005) 1111-1117
149. Yoshinobu K., Baudino L., Santiago-Raber M.L., Morito N., Dunand-Sauthier I., Morley B.J., et al. Selective up-regulation of intact, but not defective env RNAs of endogenous modified polytropic retrovirus by the Sgp3 locus of lupus-prone mice. J Immunol 182 (2009) 8094-8103
150. Tucker R.M., Roark C.L., Santiago-Raber M.L., Izui S., and Kotzin B.L. Association between nuclear antigens and endogenous retrovirus in the generation of autoantibody responses in murine lupus. Arthritis Rheum 50 (2004) 3626-3636
151. Rankin J., Boyle J.J., Rose S.J., Gabriel L., Lewis M., Thiruudaian V., et al. The Bxs6 locus of BXSB mice is sufficient for high-level expression of gp70 and the production of gp70 immune complexes. J Immunol 178 (2007) 4395-4401
152. Rhodes B., and Vyse T.J. The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford) 47 (2008) 1603-1611
153. Fernando M.M., Stevens C.R., Sabeti P.C., Walsh E.C., McWhinnie A.J., Shah A., et al. Identification of two independent risk factors for lupus within the MHC in United Kingdom families. PLoS Genet 3 (2007) e192
154. Vasconcelos C., Carvalho C., Leal B., Pereira C., Bettencourt A., Costa P.P., et al. HLA in Portuguese systemic lupus erythematosus patients and their relation to clinical features. Ann N Y Acad Sci 1173 (2009) 575-580
155. Graham R.R., Ortmann W.A., Langefeld C.D., Jawaheer D., Selby S.A., Rodine P.R., et al. Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus. Am J Hum Genet 71 (2002) 543-553
156. Ghebrehiwet B., and Peerschke E.I. Role of C1q and C1q receptors in the pathogenesis of systemic lupus erythematosus. Curr Dir Autoimmun 7 (2004) 87-97
157. Slingsby J.H., Norsworthy P., Pearce G., Vaishnaw A.K., Issler H., Morley B.J., et al. Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families. Arthritis Rheum 39 (1996) 663-670
158. Truedsson L., Bengtsson A.A., and Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 40 (2007) 560-566
159. Edberg J.C., Wu J., Langefeld C.D., Brown E.E., Marion M.C., McGwin Jr. G., et al. Genetic variation in the CRP promoter: association with systemic lupus erythematosus. Hum Mol Genet 17 (2008) 1147-1155
160. Graham R.R., Cotsapas C., Davies L., Hackett R., Lessard C.J., Leon J.M., et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 40 (2008) 1059-1061
161. Webb R., Wren J.D., Jeffries M., Kelly J.A., Kaufman K.M., Tang Y., et al. Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus. Arthritis Rheum 60 (2009) 1076-1084
162. Kariuki S.N., Moore J.G., Kirou K.A., Crow M.K., Utset T.O., and Niewold T.B. Age- and gender-specific modulation of serum osteopontin and interferon-alpha by osteopontin genotype in systemic lupus erythematosus. Genes Immun 10 (2009) 487-494
163. Han S., Guthridge J.M., Harley I.T., Sestak A.L., Kim-Howard X., Kaufman K.M., et al. Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. PLoS One 3 (2008) e0001757
164. Lee-Kirsch M.A., Gong M., Chowdhury D., Senenko L., Engel K., Lee Y.A., et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 39 (2007) 1065-1067
165. Harley J.B., arcon-Riquelme M.E., Criswell L.A., Jacob C.O., Kimberly R.P., Moser K.L., et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40 (2008) 204-210
166. Hom G., Graham R.R., Modrek B., Taylor K.E., Ortmann W., Garnier S., et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358 (2008) 900-909
167. Cunninghame Graham D.S., Vyse T.J., Fortin P.R., Montpetit A., Cai Y.C., Lim Set al. Association of LY9 in UK and Canadian SLE families. Genes Immun 9 (2008) 93-102
168. Cunninghame Graham D.S., Graham R.R., Manku H., Wong A.K., Whittaker J.C., Gaffney P.M., et al. Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nat Genet 40 (2008) 83-89
169. Thorburn C.M., Prokunina-Olsson L., Sterba K.A., Lum R.F., Seldin M.F., arcon-Riquelme M.E., et al. Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort. Genes Immun 8 (2007) 279-287
170. Lee Y.H., Woo J.H., Choi S.J., Ji J.D., and Song G.G. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis. Lupus 18 (2009) 9-15
171. Rieux-Laucat F., Le D.F., Hivroz C., Roberts I.A., Debatin K.M., Fischer A., et al. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268 (1995) 1347-1349
172. Fisher G.H., Rosenberg F.J., Straus S.E., Dale J.K., Middleton L.A., Lin A.Y., et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81 (1995) 935-946
173. Worth A., Thrasher A.J., and Gaspar H.B. Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype. Br J Haematol 133 (2006) 124-140
174. Magnusson V., Johanneson B., Lima G., Odeberg J., arcon-Segovia D., and arcon-Riquelme M.E. Both risk alleles for FcgammaRIIA and FcgammaRIIIA are susceptibility factors for SLE: a unifying hypothesis. Genes Immun 5 (2004) 130-137