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Sle3  -  systemic lupus erythmatosus susceptibility 3

Mus musculus

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Disease relevance of Sle3


High impact information on Sle3


Biological context of Sle3

  • B6.NZMc7 mice are C57BL/6 (B6) mice congenic for the NZM2410-derived chromosome 7 susceptibility interval, bearing Sle3 [8].
  • In vitro, Sle3-bearing T cells show stronger proliferation, increased expansion of CD4+ T cells, and reduced apoptosis (with or without anti-Fas) following stimulation with anti-CD3 [8].
  • We previously produced three congenic strains carrying lupus susceptibility genes (Sle1-Sle3) from the lupus-prone NZM2410 mouse on the C57BL/6 background and characterized their component phenotypes [2].

Anatomical context of Sle3

  • Thus, the NZM2410 allele of Sle3 appears to impact generalized T cell activation, and this may be causally related to the low grade, polyclonal serum autoantibodies seen in this strain [8].
  • Previous studies have shown the Sle1 locus is associated with a reduced number of regulatory T cells (Treg) and that Sle3 results in intrinsic defects of myeloid cells that hyperactivate T cells [9].

Other interactions of Sle3

  • In contrast, two locus combinations of Sle2, Sle3, and yaa failed to mediate fatal disease [2].
  • Taken together, on the nonautoimmune background, Sle3/5 affected V(H)DJ(H) junctional diversity and V(H) mutational diversity and led to recombinational activation of allelically excluded IgH genes in the periphery [10].
  • On the non-autoimmune C57BL/6 (B6) background, the chromosome 7-derived lupus susceptibility loci Sle3 and Sle5 have been shown to mediate an elevated CD4:CD8 ratio with an increase in activated CD4(+) T cells, decreased susceptibility to apoptosis, and a break in humoral tolerance [4].
  • We examined rearrangements from pre-B cells, marginal zone B cells, and follicular B cells from mice congenic for the Lbw5 (Sle3/5) lupus susceptibility loci and from other strains of mice and found very few examples of CDR3 with D-D rearrangements [11].
  • Sle3/5 is a lupus susceptibility locus identified on mouse chromosome 7 of the New Zealand Black/New Zealand White (NZB/NZW)-derived NZM2410 strain [10].

Analytical, diagnostic and therapeutic context of Sle3


  1. Epistatic modifiers of autoimmunity in a murine model of lupus nephritis. Morel, L., Tian, X.H., Croker, B.P., Wakeland, E.K. Immunity (1999) [Pubmed]
  2. Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains. Morel, L., Croker, B.P., Blenman, K.R., Mohan, C., Huang, G., Gilkeson, G., Wakeland, E.K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies. Mohan, C., Morel, L., Yang, P., Watanabe, H., Croker, B., Gilkeson, G., Wakeland, E.K. J. Clin. Invest. (1999) [Pubmed]
  4. Genetic dissection of systemic lupus erythematosus pathogenesis: evidence for functional expression of Sle3/5 by non-T cells. Sobel, E.S., Morel, L., Baert, R., Mohan, C., Schiffenbauer, J., Wakeland, E.K. J. Immunol. (2002) [Pubmed]
  5. The lupus-susceptibility locus, Sle3, mediates enhanced resistance to bacterial infections. Mehrad, B., Park, S.J., Akangire, G., Standiford, T.J., Wu, T., Zhu, J., Mohan, C. J. Immunol. (2006) [Pubmed]
  6. T cell hyperactivity in lupus as a consequence of hyperstimulatory antigen-presenting cells. Zhu, J., Liu, X., Xie, C., Yan, M., Yu, Y., Sobel, E.S., Wakeland, E.K., Mohan, C. J. Clin. Invest. (2005) [Pubmed]
  7. Cutting edge: lupus susceptibility interval Sle3/5 confers responsiveness to prolactin in C57BL/6 mice. Peeva, E., Gonzalez, J., Hicks, R., Diamond, B. J. Immunol. (2006) [Pubmed]
  8. Genetic dissection of Sle pathogenesis: Sle3 on murine chromosome 7 impacts T cell activation, differentiation, and cell death. Mohan, C., Yu, Y., Morel, L., Yang, P., Wakeland, E.K. J. Immunol. (1999) [Pubmed]
  9. IL-6 Produced by Dendritic Cells from Lupus-Prone Mice Inhibits CD4+CD25+ T Cell Regulatory Functions. Wan, S., Xia, C., Morel, L. J. Immunol. (2007) [Pubmed]
  10. Genetic dissection of lupus pathogenesis: Sle3/5 impacts IgH CDR3 sequences, somatic mutations, and receptor editing. Wakui, M., Kim, J., Butfiloski, E.J., Morel, L., Sobel, E.S. J. Immunol. (2004) [Pubmed]
  11. Paucity of V-D-D-J rearrangements and VH replacement events in lupus prone and nonautoimmune TdT-/- and TdT+/+ mice. Watson, L.C., Moffatt-Blue, C.S., McDonald, R.Z., Kompfner, E., Ait-Azzouzene, D., Nemazee, D., Theofilopoulos, A.N., Kono, D.H., Feeney, A.J. J. Immunol. (2006) [Pubmed]
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