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Profiling and genetic control of murine immunoglobulin G glycome

N-glycosylation of immunoglobulin G (IgG) shapes the immune response affecting the interactions between IgG and its ligands. Changes in the IgG N-glycan profile were observed in various physiological and pathological states. However, factors responsible for IgG N-glycome variability are not yet well defined for mouse models used to study immunity and mechanisms of diseases. To close this gap we analysed total IgG and subclass-specific Fc-linked N-glycosylation in 95 recombinant inbred mouse strains from the Collaborative Cross panel that captures 89% of known genetic variation in laboratory mice1. Observed high inter-strain variation of glycan profiles suggested strong genetic regulation of IgG N-glycome. Using quantitative trait loci analysis we discovered 5 genetic loci associated with murine IgG N-glycome and identified candidate genes, including Ighg1, Ighg2b and Ighg2c encoding the constant region of the IgG heavy chains and a glycosyltransferase gene Mgat3. Our study is the first to characterize fully the mouse IgG N-glycome and to describe IgG N-glycosylation profiles in mouse strains to aid in selection of the mouse models in the future immunological research.

mouse ; immunoglobulin G ; glycosylation ; Collaborative Cross ; genetic loci ; QTL

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