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Citations to this article

Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes.
C Mohan, … , P Yang, E K Wakeland
C Mohan, … , P Yang, E K Wakeland
Published March 15, 1998
Citation Information: J Clin Invest. 1998;101(6):1362-1372. https://doi.org/10.1172/JCI728.
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Research Article Article has an altmetric score of 5

Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes.

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Abstract

One of the hallmarks of SLE is the loss of tolerance to chromatin. The genes and mechanisms that trigger this loss of tolerance remain unknown. Our genetic studies in the NZM2410 lupus strain have implicated genomic intervals on chromosomes 1 (Sle1), 4 (Sle2), and 7 (Sle3) as conferring strong lupus susceptibility. Interestingly, B6 mice that are congenic for Sle1 (B6.NZMc1) have elevated IgG antichromatin Abs. This study explores the antinuclear antibody fine specificities and underlying cellular defects in these mice. On the B6 background, Sle1 by itself is sufficient to generate a robust, spontaneous antichromatin Ab response, staining Hep-2 nuclei homogeneously, and reacting primarily with H2A/H2B/DNA subnucleosomes. This targeted immune response peaks at 7-9 mo of age, affects both sexes with equally high penetrance (> 75%), and interestingly, does not "spread" to other subnucleosomal chromatin components. Sle1 also leads to an expanded pool of histone-reactive T cells, which may have a role in driving the anti-H2A/H2B/DNA B cells. However, these mice do not exhibit any generalized immunological defects or quantitative aberrations in lymphocyte apoptosis. We hypothesize that Sle1 may lead to the presentation of chromatin in an immunogenic fashion, or directly impact tolerance of chromatin-specific B cells.

Authors

C Mohan, E Alas, L Morel, P Yang, E K Wakeland

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 Total
Citations: 3 3 3 4 7 5 3 5 7 8 9 5 10 7 8 15 11 11 12 22 13 10 14 12 9 6 3 1 226
Citation information
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Citations to this article in year 2008 (11)

Title and authors Publication Year
Defective B-cell response to T-dependent immunization in lupus-prone mice
H Niu, ES Sobel, L Morel
European Journal of Immunology 2008
How the study of children with rheumatic diseases identified interferon-alpha and interleukin-1 as novel therapeutic targets
V Pascual, F Allantaz, P Patel, AK Palucka, D Chaussabel, J Banchereau
Immunological Reviews 2008
Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens
M Lech, OP Kulkarni, S Pfeiffer, E Savarese, A Krug, C Garlanda, A Mantovani, HJ Anders
Journal of Experimental Medicine 2008
Yaaautoimmune phenotypes are conferred by overexpression of TLR7
AM Fairhurst, S Hwang, A Wang, XH Tian, C Boudreaux, XJ Zhou, J Casco, QZ Li, JE Connolly, EK Wakeland
European Journal of Immunology 2008
Systemic IFN‐α drives kidney nephritis in B6.Sle123mice
AM Fairhurst, A Mathian, JE Connolly, A Wang, HF Gray, TA George, CD Boudreaux, XJ Zhou, QZ Li, S Koutouzov, J Banchereau, EK Wakeland
European Journal of Immunology 2008
Estrogen receptor-α deficiency attenuates autoimmune disease in (NZB × NZW)F1 mice
KK Bynoté, JM Hackenberg, KS Korach, DB Lubahn, PH Lane, KA Gould
Genes and Immunity 2008
Accelerated atherosclerosis is independent of feeding high fat diet in systemic lupus erythematosus-susceptible LDLr(-/-) mice
N Braun, NS Wade, EK Wakeland, AS Major
Lupus 2008
Genetic variation in C-reactive protein (CRP) gene may be associated with risk of systemic lupus erythematosus and CRP concentrations
PB Shih, S Manzi, P Shaw, M Kenney, AH Kao, F Bontempo, MM Barmada, C Kammerer, MI Kamboh
The Journal of rheumatology 2008
Principles of Bone Biology
CJ Rosen, T Niu
Principles of Bone Biology 2008
Accelerated atherosclerosis is independent of feeding high fat diet in systemic lupus erythematosus–susceptible LDLr−/− mice
NA Braun, NS Wade, EK Wakeland, AS Major
Lupus 2008
A lupus-susceptibility C57BL/6 locus on chromosome 3 (Sle18) contributes to autoantibody production in 129 mice
Y Heidari, L Fossati-Jimack, F Carlucci, MJ Walport, HT Cook, M Botto
Genes and Immunity 2008

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