Annals of the Rheumatic Diseases 2006;65:495-500
EXTENDED REPORT
An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus
1 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
2 Department of Pathology, Ehime University School of Medicine, Toon, Japan
Correspondence to:
Professor Masao Ono
Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba-ku, Sendai, Miyagi 980-8575, Japan; onomasao{at}mail.tains.tohoku.ac.jp
Objective: To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus.
Methods: Vasculitis of renal arteries was histopathologically evaluated in MRL/Mp-Faslpr (MRL/lpr), C57BL/6-Faslpr (B6/lpr), (MRL/lprxB6/lpr) F1, and MRL/lprx(MRL/lprxB6/lpr) F1 backcross mice. Using genomic DNA samples of the backcross mice, genome-wide scans, association studies, and linkage analyses were carried out based on genotypes of polymorphic microsatellite markers. Correlations of vasculitis grade and levels of various autoantibodies were also evaluated.
Results: Two recessive susceptibility loci of the MRL allele were identified on chromosomes 4 and 1, which had previously been defined as the autoimmune related loci termed Arvm1 and Sle-1/Nba2, respectively. The former was epistatic to the latter in a female specific manner. The titre of antinuclear autoantibody (ANA) in IgG class, but not ANA in IgM class or anti-dsDNA in either IgG or IgM class, correlated significantly with vasculitis grade.
Conclusions: The present loci have been reported in previous studies using a different set of murine strains, suggesting that they are of importance in the development of autoimmune vasculitis in murine models. The concomitance of autoimmune vasculitis and IgG ANA suggests a shared genetic factor regulating these traits.
Abbreviations: ANA, antinuclear autoantibody; QTL, quantitative trait locus; SLE, systemic lupus erythematosus
Keywords: vasculitis; autoimmunity; genetics; mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
- Full Text
- Full Text (PDF)
-
All Versions of this Article:
ard.2005.040832v1
65/4/495 most recent - Submit a response
- Alert me when this article is cited
- Alert me when eLetters are posted
- Alert me if a correction is posted
- Citation Map
Services
- Email this link to a friend
- Similar articles in this journal
- Similar articles in PubMed
- Add article to my folders
- Download to citation manager
- Request Permissions
Citing Articles
Google Scholar
PubMed
Topic Collections
Bookmark with
Register for free content
The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.
Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.
