Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein

Susan A. Boackle, V. Michael Holers, Xiaojiang Chen, Gerda Szakonyi, David R. Karp, Edward K. Wakeland, Laurence Morel

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

The major murine systemic lupus erythematosus (SLE) susceptibility locus, Sle1, corresponds to three loci independently affecting loss of tolerance to chromatin in the NZM2410 mouse. The congenic interval corresponding to Sle1c contains Cr2, which encodes complement receptors 1 and 2 (CR1/CR2, CD35/CD21). NZM2410/NZW Cr2 exhibits a single nucleotide polymorphism that introduces a novel glycosylation site, resulting in higher molecular weight proteins. This polymorphism, located in the C3d binding domain, reduces ligand binding and receptor-mediated cell signaling. Molecular modeling based on the recently solved CR2 structure in complex with C3d reveals that this glycosylation interferes with receptor dimerization. These data demonstrate a functionally significant phenotype for the NZM2410 Cr2 allele and strongly support its role as a lupus susceptibility gene.

Original languageEnglish (US)
Pages (from-to)775-785
Number of pages11
JournalImmunity
Volume15
Issue number5
DOIs
Publication statusPublished - 2001

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this