Stanley Pamela
Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA.
J Mol Biol. 2016 Aug 14;428(16):3166-3182. doi: 10.1016/j.jmb.2016.03.025. Epub 2016 Mar 31.
There are five major classes of glycan including N- and O-glycans, glycosaminoglycans, glycosphingolipids, and glycophosphatidylinositol anchors, all expressed at the molecular frontier of each mammalian cell. Numerous biological consequences of altering the expression of mammalian glycans are understood at a mechanistic level, but many more remain to be characterized. Mouse mutants with deleted, defective, or misexpressed genes that encode activities necessary for glycosylation have led the way to identifying key functions of glycans in biology. However, with the advent of exome sequencing, humans with mutations in genes involved in glycosylation are also revealing specific requirements for glycans in mammalian development. The aim of this review is to summarize glycosylation genes that are necessary for mouse embryonic development, pathway-specific glycosylation genes whose deletion leads to postnatal morbidity, and glycosylation genes for which effects are mild, but perturbation of the organism may reveal functional consequences. General strategies for generating and interpreting the phenotype of mice with glycosylation defects are discussed in relation to human congenital disorders of glycosylation (CDG).
聚糖主要有五大类，包括N-聚糖和O-聚糖、糖胺聚糖、糖鞘脂和糖基磷脂酰肌醇锚定物，所有这些都在每个哺乳动物细胞的分子前沿表达。在分子机制层面，人们已经了解了改变哺乳动物聚糖表达的许多生物学后果，但仍有更多有待表征。编码糖基化所需活性的基因缺失、有缺陷或表达错误的小鼠突变体，为确定聚糖在生物学中的关键功能指明了方向。然而，随着外显子组测序的出现，糖基化相关基因突变的人类也揭示了聚糖在哺乳动物发育中的特定需求。本综述的目的是总结小鼠胚胎发育所必需的糖基化基因、缺失后会导致出生后发病的特定途径糖基化基因，以及那些影响轻微但对生物体的干扰可能会揭示功能后果的糖基化基因。结合人类先天性糖基化障碍（CDG），讨论了产生和解释糖基化缺陷小鼠表型的一般策略。
