Profiling and genetic control of the murine immunoglobulin G glycome

Jasminka Krištić, Olga O. Zaytseva, Ramesh Ram, Quang Nguyen, Mislav Novokmet, Frano Vučković, Marija Vilaj, Irena Trbojević-Akmačić, Marija Pezer, Kathleen M. Davern, Grant Morahan, Gordan Lauc

Index: 10.1038/s41589-018-0034-3

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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.