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Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice.
S Vidal, … , D H Kono, A N Theofilopoulos
S Vidal, … , D H Kono, A N Theofilopoulos
Published February 1, 1998
Citation Information: J Clin Invest. 1998;101(3):696-702. https://doi.org/10.1172/JCI1817.
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Research Article

Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice.

Abstract

Background genes determine the incidence and severity of lymphoaccumulation and histopathologic manifestations of systemic autoimmunity in mice homozygous for the apoptosis-defective Faslpr mutation. By interval mapping of 274 F2 mice intercrossed between MRL-Faslpr (severe disease) and C57BL/6-Faslpr (minimal disease), four loci were identified with significant linkage to lymphadenopathy and/ or splenomegaly on chromosomes 4, 5, 7, and 10, which were named lupus in (MRL-Faslpr x B6-Faslpr)F2 cross1-4 (Lmb1-4), respectively. Lmb1, -2, and -3 were also linked to the production of anti-dsDNA antibodies, but not glomerulonephritis, whereas Lmb4 was associated with glomerulonephritis. Lmb2, -3, and -4 were inherited from the MRL background, but interestingly, Lmb1 was derived from the C57BL16-Faslpr. Nevertheless, each locus, regardless of the strain of origin, appeared to act in an additive manner, although certain combinations were more effective. Only a single suggestive locus on chromosome 1 could be correlated with arthritis. The identification of loci with highly significant linkage to disease manifestations in Faslpr strains will make it possible to map and clone new genetic defects contributing to autoimmunity.

Authors

S Vidal, D H Kono, A N Theofilopoulos

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JA Kelly, KL Moser, JB Harley 		Genes and Immunity 2002
T-cell signalling and autoimmunity: molecular mechanisms of disease
PS Ohashi 		Nature Reviews Immunology 2002
Use of Genetic Knockouts to Modulate Disease Expression in a Murine Model of Lupus, MRL/lpr Mice
CM Reilly, GS Gilkeson 		Immunologic Research 2002
The NOD Mouse as a Model of SLE
PA Silveira, AG Baxter 		Autoimmunity 2001
Autoimmune Lymphoproliferative Syndrome Type III: An Indefinite Disorder
JV der Bosch, J Otten, K Thielemans 		Leukemia & Lymphoma 2001
Autoimmune Lymphoproliferative Syndrome Type III, an Indefinite Disorder
JD Bosch, J Otten, K Thielemans 		Leukemia & Lymphoma 2001
Delineating the Genetic Basis of Systemic Lupus Erythematosus
EK Wakeland, K Liu, RR Graham, TW Behrens 		Immunity 2001
CD4(+) T cells from lupus-prone mice are hyperresponsive to T cell receptor engagement with low and high affinity peptide antigens: a model to explain spontaneous T cell activation in lupus
GS Vratsanos, S Jung, YM Park, J Craft 		Journal of Experimental Medicine 2001
Murine lupus genetics: lessons learned
C Mohan 		Current Opinion in Rheumatology 2001
Genetic Dissection of Age-Related Changes of Immune Function in Mice
JD Mountz, GE van Zant, HG Zhang, WE Grizzle, R Ahmed, RW Williams, HC Hsu 		Scandinavian Journal of Immunology 2001
Abnormal IgG galactosylation and arthritis in MRL-Faslpr or MRL-FasLgld mice are under the control of the MRL genetic background
Y Kuroda, M Nakata, M Nose, N Kojima, T Mizuochi 		FEBS Letters 2001
Inflammatory Diseases of Blood Vessels
G Hansson 		Inflammatory Diseases of Blood Vessels: A Dialogue Between the Artery and the Immune System 2001
Suggestive Evidence for Association of Human Chromosome 18q12-q21 and Its Orthologue on Rat and Mouse Chromosome 18 With Several Autoimmune Diseases
TR Merriman, HJ Cordell, IA Eaves, PA Danoy, F Coraddu, R Barber, F Cucca, S Broadley, S Sawcer, A Compston, P Wordsworth, J Shatford, S Laval, J Jirholt, R Holmdahl, AN Theofilopoulos, DH Kono, J Tuomilehto, E Tuomilehto-Wolf, R Buzzetti, MG Marrosu, DE Undlien, KS Ronningen, C Ionesco-Tirgoviste, JP Shield, F Pociot, J Nerup, CO Jacob, C Polychronakos, SC Bain, JA Todd 		Diabetes 2001
Cd4 + T Cells from Lupus-Prone Mice Are Hyperresponsive to T Cell Receptor Engagement with Low and High Affinity Peptide Antigens: A Model to Explain Spontaneous T Cell Activation in Lupus
GS Vratsanos, S Jung, YM Park, J Craft 		Journal of Experimental Medicine 2001
Mechanisms of Lymphocyte Activation and Immune Regulation VIII
S Gupta 		2001
Genetic Contributions of Nonautoimmune SWR Mice Toward Lupus Nephritis
S Xie, SH Chang, P Yang, C Jacob, A Kaliyaperumal, SK Datta, C Mohan 		Journal of immunology (Baltimore, Md. : 1950) 2001
Anti-Sm B Cell Differentiation in Ig Transgenic MRL/Mp- lpr / lpr Mice: Altered Differentiation and an Accelerated Response
S Santulli-Marotto, Y Qian, S Ferguson, SH Clarke 		Journal of immunology (Baltimore, Md. : 1950) 2001
Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells
ML Fields, CL Sokol, A Eaton-Bassiri, S Seo, MP Madaio, J Erikson 		Journal of immunology (Baltimore, Md. : 1950) 2001
Fas-mediated apoptosis in clinical remissions of relapsing experimental autoimmune encephalomyelitis
GC Suvannavejh, MC Canto, LA Matis, SD Miller 		Journal of Clinical Investigation 2000
Are animal models of vasculitis suitable tools?
U Specks 		Current Opinion in Rheumatology 2000
Lessons from the NZM2410 Model and Related Strains
L Morel, EK Wakeland 		International Reviews of Immunology 2000
Genetic Basis of the Complex Pathological Manifestations of Collagen Disease: Lessons from MRL/lpr and Related Mouse Models
M Nose, M Nishihara, H Fujii 		International Reviews of Immunology 2000
Genetics of Systemic Autoimmunity in Mouse Models of Lupus
DH Kono, AN Theofilopouuos 		International Reviews of Immunology 2000
The pathogenesis of autoimmunity in New Zealand
A Borchers, AA Ansari, T Hsu, DH Kono, ME Gershwin 		Seminars in Arthritis and Rheumatism 2000
A Susceptibility Locus for Human Systemic Lupus Erythematosus (hSLE1) on Chromosome 2q
AK Lindqvist, K Steinsson, B Johanneson, H Kristjánsdóttir, A Àrnasson, G Gröndal, I Jonasson, V Magnusson, G Sturfelt, L Truedsson, E Svenungsson, I Lundberg, JD Terwilliger, UB Gyllensten, ME Alarcón-Riquelme 		Journal of Autoimmunity 2000
Spontaneous Autoimmune Disease in FcγRIIB-Deficient Mice Results from Strain-Specific Epistasis
S Bolland, JV Ravetch 		Immunity 2000
Are animal models of vasculitis suitable tools?:
U Specks 		Current Opinion in Rheumatology 2000
Nosocomial Pneumonia
UL Specks 		Nosocomial Pneumonia 2000
Genetic factors influencing the development of chronic graft-versus-host disease in a murine model
DL Slayback, JA Dobkins, JM Harper, RD Allen 		Bone Marrow Transplantation 2000
The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity
RM Siegel, FK Chan, HJ Chun, MJ Lenardo 		Nature Immunology 2000
Modulation of Renal Disease in MRL/ lpr Mice Genetically Deficient in the Alternative Complement Pathway Factor B
H Watanabe, G Garnier, A Circolo, RA Wetsel, P Ruiz, VM Holers, SA Boackle, HR Colten, GS Gilkeson 		Journal of immunology (Baltimore, Md. : 1950) 2000
A Genome Scan Using a Novel Genetic Cross Identifies New Susceptibility Loci and Traits in a Mouse Model of Rheumatoid Arthritis
JM Otto, R Chandrasekeran, C Vermes, K Mikecz, A Finnegan, SE Rickert, JT Enders, TT Glant 		Journal of immunology (Baltimore, Md. : 1950) 2000
Linkage Analysis of Systemic Lupus Erythematosus Induced in Diabetes-Prone Nonobese Diabetic Mice by Mycobacterium bovis
MA Jordan, PA Silveira, DP Shepherd, C Chu, SJ Kinder, J Chen, LJ Palmisano, LD Poulton, AG Baxter 		Journal of immunology (Baltimore, Md. : 1950) 2000
Genetic Studies in Systemic Autoimmunity and Aging
DH Kono, AN Theofilopoulos 		Immunologic Research 2000
Regulation of autoreactive anti-IgG (Rheumatoid Factor) B cells in normal and autoimmune mice
H Wang, MJ Shlomchik 		Immunologic Research 1999
Control of separate pathogenic autoantibody responses marks MHC gene contributions to murine lupus
TJ Vyse, RK Halterman, SJ Rozzo, S Izui, BL Kotzin 		Proceedings of the National Academy of Sciences 1999
Autoantigen-specific B cell activation in Fas-deficient rheumatoid factor immunoglobulin transgenic mice
H Wang, MJ Shlomchik 		Journal of Experimental Medicine 1999
MRL-lpr/lpr mice exhibit a defect in maintaining developmental arrest and follicular exclusion of anti-double-stranded DNA B cells
L Mandik-Nayak, SJ Seo, C Sokol, KM Potts, A Bui, J Erikson 		Journal of Experimental Medicine 1999
Structure and Function of Fas/Fas Ligand
JR Orlinick, AK Vaishnaw, KB Elkon 		International Reviews of Immunology 1999
The Genes of Systemic Autoimmunity
AN Theofilopoulos, DH Kono 		Proceedings of The Association of American Physicians 1999
Mapping autoimmunity genes
MM Griffiths, JA Encinas, EF Remmers, VK Kuchroo, RL Wilder 		Current Opinion in Immunology 1999
MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti-double-stranded DNA B Cells
L Mandik-Nayak, S Seo, C Sokol, KM Potts, A Bui, J Erikson 		Journal of Experimental Medicine 1999
Autoantigen-Specific B Cell Activation in FAS-Deficient Rheumatoid Factor Immunoglobulin Transgenic Mice
H Wang, MJ Shlomchik 		Journal of Experimental Medicine 1999
Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment
M Lenardo, KM Chan, F Hornung, H McFarland, R Siegel, J Wang, L Zheng 		Annual Review of Immunology 1999
Aberrant Wound Healing and TGF-β Production in the Autoimmune-Prone MRL/+ Mouse
JA Kench, DM Russell, VA Fadok, SK Young, GS Worthen, J Jones-Carson, JE Henson, PM Henson, D Nemazee 		Clinical Immunology 1999
Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis
JM Otto, G Cs-Szab, J Gallagher, S Velins, K Mikecz, EI Buzs, JT Enders, Y Li, BR Olsen, TT Glant 		Arthritis & Rheumatism 1999
Genetic basis of autoimmune sialadenitis in MRL/lpr lupus-prone mice: Additive and hierarchical properties of polygenic inheritance
M Nishihara, M Terada, J Kamogawa, Y Ohashi, S Mori, S Nakatsuru, Y Nakamura, M Nose 		Arthritis & Rheumatism 1999
A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families
PM Gaffney, GM Kearns, KB Shark, WA Ortmann, SA Selby, ML Malmgren, KE Rohlf, TC Ockenden, RP Messner, RA King, SS Rich, TW Behrens 		Proceedings of the National Academy of Sciences 1998
Mechanisms and Genetics of Autoimmunitya
AN Theofilopoulos, DH Kono 		Annals of the New York Academy of Sciences 1998
Genetics of susceptibility to chronic experimental encephalomyelitis and arthritis
R Holmdahl 		Current Opinion in Immunology 1998
La contribution des modèles murins à la compréhension des maladies immunitaires
L Morel, ME Yui, EK Wakeland 		Annales de l'Institut Pasteur/Actualités 1998
Effector and predisposing genes in murine lupus
AN Theofilopoulos 		Lupus 1998

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