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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 2011 (7)

Title and authors Publication Year
Caspase-Activated DNase is Required to Maintain Tolerance to Lupus Nuclear AutoAntigens
NR Jog, L Frisoni, Q Shi, M Monestier, S Hernandez, J Craft, ET Prak, R Caricchio
Arthritis & Rheumatism 2011
Murine Models of Systemic Lupus Erythematosus
D Perry, A Sang, Y Yin, YY Zheng, L Morel
Journal of Biomedicine and Biotechnology 2011
A novel isoform of the Ly108 gene ameliorates murine lupus
M Keszei, C Detre, ST Rietdijk, P Muñoz, X Romero, SB Berger, S Calpe, G Liao, W Castro, A Julien, YY Wu, DM Shin, J Sancho, M Zubiaur, HC 3rd, L Morel, P Engel, N Wang, C Terhorst
Journal of Experimental Medicine 2011
Cutting Edge: An NK Cell-Independent Role for Slamf4 in Controlling Humoral Autoimmunity
DR Brown, S Calpe, M Keszei, N Wang, S McArdel, C Terhorst, AH Sharpe
Journal of immunology (Baltimore, Md. : 1950) 2011
A New Zealand Black-derived locus suppresses chronic graft-versus-host disease and autoantibody production through nonlymphoid bone marrow-derived cells
Z Xu, A Vallurupalli, C Fuhrman, D Ostrov, L Morel
Journal of immunology (Baltimore, Md. : 1950) 2011
Murine Lupus Susceptibility Locus Sle2 Activates DNA-Reactive B Cells through Two Sub-Loci with Distinct Phenotypes
L Zeumer, A Sang, H Niu, L Morel
Genes and Immunity 2011
Auto-antibody production and glomerulonephritis in congenic Slamf1−/− and Slamf2−/− [B6.129] but not in Slamf1−/− and Slamf2−/− [BALB/c.129] mice
M Keszei, YE Latchman, VK Vanguri, DR Brown, C Detre, M Morra, CV Arancibia-Carcamo, CV Arancibia, E Paul, S Calpe, W Castro, N Wang, C Terhorst, AH Sharpe
International Immunology 2011

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