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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 2009 (15)

Title and authors Publication Year
Development of murine lupus involves the combined genetic contribution of the SLAM and FcgammaR intervals within the Nba2 autoimmune susceptibility locus
TN Jørgensen, J Alfaro, HL Enriquez, C Jiang, WM Loo, S Atencio, MR Bupp, CM Mailloux, T Metzger, S Flannery, SJ Rozzo, BL Kotzin, M Rosemblatt, MR Bono, LD Erickson
Journal of immunology (Baltimore, Md. : 1950) 2009
CXCR4/CXCL12 hyperexpression plays a pivotal role in the pathogenesis of lupus
A Wang, AM Fairhurst, K Tus, S Subramanian, Y Liu, F Lin, P Igarashi, XJ Zhou, F Batteux, D Wong, EK Wakeland, C Mohan
Journal of immunology (Baltimore, Md. : 1950) 2009
The lupus susceptibility locus Sle3 is not sufficient to accelerate atherosclerosis in lupus-susceptible low density lipoprotein receptor-deficient mice
NS Wade, BG Stevenson, DS Dunlap, AS Major
Lupus 2009
Antigen receptor signaling in the rheumatic diseases
J Zikherman, A Weiss
Arthritis Research & Therapy 2009
The lupus-susceptibility gene kallikrein downmodulates antibody-mediated glomerulonephritis
QZ Li, J Zhou, R Yang, M Yan, Q Ye, K Liu, S Liu, X Shao, L Li, XJ Zhou, EK Wakeland, C Mohan
Genes and Immunity 2009
Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus
CO Jacob, J Zhu, DL Armstrong, M Yan, J Han, XJ Zhou, JA Thomas, A Reiff, BL Myones, JO Ojwang, KM Kaufman, M Klein-Gitelman, D McCurdy, L Wagner-Weiner, E Silverman, J Ziegler, JA Kelly, JT Merrill, JB Harley, R Ramsey-Goldman, LM Vila, SC Bae, TJ Vyse, GS Gilkeson, PM Gaffney, KL Moser, CD Langefeld, R Zidovetzki, C Mohan
Proceedings of the National Academy of Sciences 2009
Anti-nuclear antibody reactivity in lupus may be partly hard-wired into the primary B-cell repertoire
S Chang, L Yang, YM Moon, YG Cho, SY Min, TJ Kim, YJ Kim, W Patrick, HY Kim, C Mohan
Molecular Immunology 2009
Molecular hallmarks of anti-chromatin antibodies associated with the lupus susceptibility locus, Sle1
Z Liang, S Chang, MS Youn, C Mohan
Molecular Immunology 2009
The Lupus Susceptibility Locus Sle1 Breaches Peripheral B Cell Tolerance at the Antibody-Forming Cell and Germinal Center Checkpoints
R Vuyyuru, C Mohan, T Manser, ZS Rahman
Journal of immunology (Baltimore, Md. : 1950) 2009
Effects of the Sri Lankan medicinal plant, Salacia reticulata, in rheumatoid arthritis
Y Sekiguchi, H Mano, S Nakatani, J Shimizu, M Wada
Genes & Nutrition 2009
Interleukin-6 aborts lymphopoiesis and elevates production of myeloid cells in systemic lupus erythematosus-prone B6.Sle1.Yaa animals
K Maeda, A Malykhin, BN Teague-Weber, XH Sun, AD Farris, KM Coggeshall
Blood 2009
Activation-induced deaminase heterozygous MRL/lpr mice are delayed in the production of high-affinity pathogenic antibodies and in the development of lupus nephritis
C Jiang, ML Zhao, M Diaz
Immunology 2009
Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral amplification by innate immunity and end-organ inflammation
H Kanta, C Mohan
Genes and Immunity 2009
BLyS Ligands and Receptors
MP Cancro
2009
The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies
K Hannestad, H Scott
Journal of immunology (Baltimore, Md. : 1950) 2009

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