Profiling and genetic control of the murine immunoglobulin G glycome

Profiling and genetic control of the murine immunoglobulin G glycome
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DOI:
10.1038/s41589-018-0034-3
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发表时间:
2018-05-01
影响因子:
14.8
通讯作者:
Lauc, Gordan
Lauc, Gordan
中科院分区:
生物学1区
文献类型:
--
作者:
Kristic, Jasminka;Zaytseva, Olga O.;Lauc, Gordan

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免疫球蛋白G(IgG)糖基化对免疫系统的功能至关重要,但其个体间变异性的遗传和环境因素尚未得到很好的定义。协作杂交(CC)遗传资源利用了小鼠90%以上的常见遗传变异。通过分析95个CC菌株的IgG糖组组成,我们进行了几个重要的观察:(i)尽管所有小鼠具有相同的环境影响,但小鼠菌株之间的糖组变异高于个体人类之间的糖组变异;(ii)发现五个遗传基因座与鼠IgG糖基化相关;(iii)传统糖基化位点基序之外的变体影响糖组变异;(iv)等分N-乙酰葡糖胺(GlcNAc)由几种菌株产生,尽管大多数先前的研究已经报道在鼠IgG上不存在含有等分GlcNAc的聚糖;和(v)普通实验室小鼠菌株不是研究糖基化对IgG功能的影响的最佳动物模型。
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.