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

Producción científica: Articlerevisión exhaustiva

190 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)775-785
Número de páginas11
PublicaciónImmunity
Volumen15
N.º5
DOI
EstadoPublished - 2001
Publicado de forma externa

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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