Profiling and genetic control of the murine immunoglobulin G glycome

J. Krištić, O.O. Zaytseva, R. Ram, Q. Nguyen, M. Novokmet, F. Vučković, M. Vilaj, I. Trbojević-Akmačić, M. Pezer, K.M. Davern, G. Morahan, G. Lauc

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Immunoglobulin G (IgG) glycosylation is essential for function of the immune system, but the genetic and environmental factors that underlie its inter-individual variability are not well defined. The Collaborative Cross (CC) genetic resource harnesses over 90% of the common genetic variation of the mouse. By analyzing the IgG glycome composition of 95 CC strains, we made several important observations: (i) glycome variation between mouse strains was higher than between individual humans, despite all mice having the same environmental influences; (ii) five genetic loci were found to be associated with murine IgG glycosylation; (iii) variants outside traditional glycosylation site motifs affected glycome variation; (iv) bisecting N-acetylglucosamine (GlcNAc) was produced by several strains although most previous studies have reported the absence of glycans containing the bisecting GlcNAc on murine IgGs; and (v) common laboratory mouse strains are not optimal animal models for studying effects of glycosylation on IgG function.

Original languageEnglish
Pages (from-to)516-524
Number of pages9
JournalNature Chemical Biology
Volume14
Issue number5
DOIs
Publication statusPublished - 1 May 2018

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