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Over-expression of the bovine FcRn in the mammary gland results in increased IgG levels in both milk and serum of transgenic mice

机译:牛FcRn在乳腺中的过表达导致转基因小鼠的牛奶和血清中IgG水平升高

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摘要

The neonatal Fc receptor (FcRn) protects immunoglobulin G (IgG) from catabolism and is also responsible for IgG absorption in the neonatal small intestine. However, whether it mediates the transfer of IgG from plasma to milk still remains speculative. In the present study, we have generated transgenic mice that over-express the bovine FcRn (bFcRn) in their lactating mammary glands. Significantly increased IgG levels were observed in the sera and milk from transgenic animals, suggesting that the over-expressed bFcRn could bind and protect endogenous mouse IgG and thus extend its lifespan. We also found that injected human IgG showed a significantly longer half-life (7–8 days) in the transgenic mice than in controls (2·9 days). Altogether, the data suggested that bFcRn could bind both mouse and human IgG, showing a cross-species FcRn–IgG binding activity. However, we found no selective accumulation of endogenous mouse IgG or injected bovine IgG in the milk of the transgenic females, supporting a previous hypothesis that IgG was transported from serum to milk in an inverse correlation to its binding affinity to FcRn.
机译:新生儿Fc受体(FcRn)保护免疫球蛋白G(IgG)免于分解代谢,并且还负责新生儿小肠中IgG的吸收。但是,它是否介导IgG从血浆向乳汁的转移仍然是推测性的。在本研究中,我们已经产生了在哺乳期乳腺中过表达牛FcRn(bFcRn)的转基因小鼠。在转基因动物的血清和牛奶中观察到IgG水平显着增加,这表明过表达的bFcRn可以结合并保护内源性小鼠IgG,从而延长其寿命。我们还发现,注射的人IgG在转基因小鼠中的半衰期(7-8天)比对照组(2·9天)长得多。总之,数据表明bFcRn可以结合小鼠和人的IgG,显示出跨物种的FcRn-IgG结合活性。但是,我们没有发现内源性小鼠IgG或注射的牛IgG在转基因雌性小鼠的乳汁中有选择性的积累,支持了以前的假设,即IgG从血清运输到乳汁中与其与FcRn的结合亲和力成反比。

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