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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 2006 (12)

Title and authors Publication Year
The lupus-susceptibility locus, Sle3, mediates enhanced resistance to bacterial infections
B Mehrad, SJ Park, G Akangire, TJ Standiford, T Wu, J Zhu, C Mohan
Journal of immunology (Baltimore, Md. : 1950) 2006
Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus
AK Stanic, CM Stein, AC Morgan, S Fazio, MR Linton, EK Wakeland, NJ Olsen, AS Major
Proceedings of the National Academy of Sciences 2006
Development and Selection of Edited B Cells in B6.56R Mice
DR Sekiguchi, L Yunk, D Gary, D Charan, B Srivastava, D Allman, MG Weigert, ET Prak
Journal of immunology (Baltimore, Md. : 1950) 2006
Role of TLR9 in Anti-Nucleosome and Anti-DNA Antibody Production in lpr Mutation-Induced Murine Lupus
A Lartigue, P Courville, I Auquit, A François, C Arnoult, F Tron, D Gilbert, P Musette
Journal of immunology (Baltimore, Md. : 1950) 2006
A Tlr7 translocation accelerates systemic autoimmunity in murine lupus
S Subramanian, K Tus, QZ Li, A Wang, XH Tian, J Zhou, C Liang, G Bartov, LD McDaniel, XJ Zhou, RA Schultz, EK Wakeland
Proceedings of the National Academy of Sciences 2006
Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes
ME Haywood, SJ Rose, S Horswell, MJ Lees, G Fu, MJ Walport, BJ Morley
Genes and Immunity 2006
Dynamics of Bone and Cartilage Metabolism
JE Mulder, CA Kulak, E Shane
Dynamics of Bone and Cartilage Metabolism 2006
A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice
H Komori, H Furukawa, S Mori, MR Ito, M Terada, MC Zhang, N Ishii, N Sakuma, M Nose, M Ono
Journal of immunology (Baltimore, Md. : 1950) 2006
Effects of arginine-vasopressin and parathyroid hormone-related protein (1–34) on cell proliferation and production of YKL-40 in cultured chondrocytes from patients with rheumatoid arthritis and osteoarthritis
M Petersson, E Bucht, B Granberg, A Stark
Osteoarthritis and Cartilage 2006
Environment versus genetics in autoimmunity: a geneticist's perspective
C Mohan
Lupus 2006
Regulation of B Cell Tolerance by the Lupus Susceptibility Gene Ly108
KR Kumar, L Li, M Yan, M Bhaskarabhatla, AB Mobley, C Nguyen, JM Mooney, JD Schatzle, EK Wakeland, C Mohan
Science 2006
Hypercalcemia in rheumatoid arthritis: relationship with disease activity and bone metabolism
P Oelzner, G Lehmann, T Eidner, S Franke, A Müller, G Wolf, G Hein
Rheumatology International 2006

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