甘露聚糖结合凝集素（MBL）基因突变引起免疫缺损的机理未明。本项目拟采用SDM-PCR技术，构建GGC54GAC MBL突变体，转染CHO细胞，对照研究其基因转录、蛋白合成泌、多聚化程度、体内半衰期、激活补体及与ClqR结合而介导吞噬等生物学行为，.揭示MBL缺损的发』恚萌彼鸬恼锒嫌胫瘟蒲芯刻峁├砺酆褪笛橐谰荩⒂兄诶斫釳BL精细的结构-功芄叵怠?.....................

Mannan-binding lectin(MBL), a member of the collectin family of proteins, plays a key role in the innate host defense. It recognizes carbohydrate structures on microbial surfaces, whereupon MBL-associated serine proteinases-1 and -2 initiate the complement cascade by the lectin pathway, and opsonization of microorganisms by MBL leads to phagocytosis mediated by cell surface collectin receptors on phagocytes, resulting in microorganism destruction. Low serum concentration of MBL is the basis for a common opsonic deficiency, predisposing patients to infections, and caused by three point mutations in the MBL gene, but the mechanisms underlying the immunodeficiency are poorly understood. In this study, the GGC54GAC human MBL mutant was constructed and expressed in CHO cells and the effects of the mutation was studied. The GGC54GAC MBL mRNA was expressed and mutant MBL protein secreted into the medium almost at the same level as the wild-type MBL, but the formation of higher multimers and the half-life in animals were interfered with significantly. The abilities of the mutant MBL protein to bind to MBL associated serine protease-1/2 and activate the complement system and to bind the collectin receptors on phagocytes and mediate opsonophagocytosis were decreased compared with the wild-type MBL protein. These data shown that the GGC54GAC mutation has no significant effect on the gene expression and protein secretion of MBL, but the change in the oligomer composition can lead to increased turnover from the serum and account for the reduction in the biological activities. The understanding of the molecular mechanisms for MBL deficiency can lay solid foundations for studies on the diagnosis and treatment of the deficiency.