An allelic variant of Crry in the murine Sle1c lupus susceptibility interval is not impaired in its ability to regulate complement activation

Svetlana N. Tchepeleva, Joshua M. Thurman, Katherine Ruff, Stephen J. Perkins, Laurence Morel, Susan A. Boackle

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The Sle1c subinterval on distal murine chromosome 1 confers loss of tolerance to chromatin. Cr2, which encodes complement receptors 1 and 2 (CR1/CR2; CD35/CD21), is a strong candidate gene for lupus susceptibility within this interval based on structural and functional alterations in its protein products. CR1-related protein/gene Y (Crry) lies 10 kb from Cr2 and encodes a ubiquitously expressed complement regulatory protein that could also play a role in the pathogenesis of systemic lupus erythematosus. Crry derived from B6.Sle1c congenic mice migrated at a higher m.w. by SDS-PAGE compared with B6 Crry, as a result of differential glycosylation. A single-nucleotide polymorphism in the first short consensus repeat of Sle1c Crry introduced a novel N-linked glycosylation site likely responsible for this structural alteration. Five additional single-nucleotide polymorphisms in the signal peptide and short consensus repeat 1 of Sle1c Crry were identified. However, the cellular expression of B6 and B6.Sle1c Crry and their ability to regulate the classical pathway of complement were not significantly different. Although soluble Sle1c Crry regulated the alternative pathway of complement more efficiently than B6 Crry, as a membrane protein, it regulated the alternative pathway equivalently to B6 Crry. These data fail to provide evidence for a functional effect of the structural alterations in Sle1c Crry and suggest that the role of Cr2 in the Sle1c autoimmune phenotypes can be isolated in recombinant congenic mice containing both genes.

Original languageEnglish (US)
Pages (from-to)2331-2339
Number of pages9
JournalJournal of Immunology
Volume185
Issue number4
DOIs
StatePublished - Aug 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'An allelic variant of Crry in the murine Sle1c lupus susceptibility interval is not impaired in its ability to regulate complement activation'. Together they form a unique fingerprint.

Cite this