The Journal of Experimental Medicine
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 29 April 2002 doi:10.1084/jem.20020165
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bolland, S.
Right arrow Articles by Ravetch, J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bolland, S.
Right arrow Articles by Ravetch, J. V.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*UniSTS
Medline Plus Health Information
*Lupus
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2002/5/1167/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 9, May 6, 2002 1167-1174
Genetic Modifiers of Systemic Lupus Erythematosus in Fc{gamma}RIIB-/- Mice

Silvia Bolland1, Young-Sun Yim2, Katalin Tus2, Edward K. Wakeland2 and Jeffrey V. Ravetch1

1 Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021
2 Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235

Address correspondence to J.V. Ravetch, Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: 212-327-7321; Fax: 212-327-7318; E-mail: ravetch{at}rockefeller.edu

Fc{gamma}RIIB is a potent lupus susceptibility gene as demonstrated by the observation that mice deficient in this molecule develop spontaneous antinuclear antibodies (ANA) and fatal glomerulonephritis when on the C57BL/6 background. To determine the mechanisms underlying the epistasis displayed by this gene we have constructed hybrids between Fc{gamma}RIIB-/- and the systemic lupus erythematosus (SLE) modifiers yaa and lpr and the susceptibility locus Sle1. Sle1 and B6.RIIB-/- are both physically and functionally coupled; compound heterozygotes of Sle1 and B6.RIIB-/- develop significant disease, while single heterozygotes display no evidence of autoimmunity or disease, indicating that these genes lie on the same genetic pathway resulting in the loss of tolerance to nuclear antigens. However, the generation of ANA in itself is insufficient to account for the severity of autoimmune disease in this model, as demonstrated by analysis of yaa and lpr hybrids. Thus, B6.RIIB-/-/lpr mice are protected from disease progression, despite equivalent titers of ANA. In contrast, B6.RIIB-/-/yaa mice have significantly enhanced disease despite reduced ANA titers. Yaa modifies the specificity and thus the pathogenicity of the B6. RIIB-/- ANA, by converting them to antinucleolar antibodies. In addition to these known modifier pathways, we have discovered two novel, recessive loci contributed by the C57BL/6 genome that are required for the ANA phenotype, further indicating the epistatic properties of this SLE model.

Key Words: lpr • yaa • Sle1 • autoantibodies • glomerulonephritis


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS