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Transgenic Cows That Produce Recombinant Human Lactoferrin in Milk Are Not Protected from Experimental Escherichia coli Intramammary Infection

机译:在牛奶中产生重组人乳铁蛋白的转基因奶牛没有受到实验性大肠杆菌的乳房内感染的保护

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This is the first study describing an experimental mastitis model using transgenic cows expressing recombinant human lactoferrin (rhLf) in their milk. The aim of the study was to investigate the concentrations in milk and protective effects of bovine and recombinant human lactoferrin in experimental Escherichia coli mastitis. Experimental intramammary infection was induced in one udder quarter of seven first-lactating rhLf-transgenic cows and six normal cows, using an E. coli strain isolated from cows with clinical mastitis and known to be susceptible to Lf in vitro. Clinical signs were recorded during the experimental period, concentrations of human and bovine Lf and indicators of inflammation and bacterial counts were determined for milk, and concentrations of acute-phase proteins and tumor necrosis factor alpha were determined for sera and milk. Serum cortisol and blood hematological and biochemical parameters were also determined. Expression levels of rhLf in the milk of transgenic cows remained constant throughout the experiment (mean, 2.9 mg/ml). The high Lf concentrations in the milk of transgenic cows did not protect them from intramammary infection. All cows became infected and developed clinical mastitis. The rhLf-transgenic cows showed milder systemic signs and lower serum cortisol and haptoglobin concentrations than did controls. This may be explained by lipopolysaccharide-neutralizing and immunomodulatory effects of the high Lf concentrations in their milk. However, Lf does not seem to be a very efficient protein for genetic engineering to enhance the mastitis resistance of dairy cows.
机译:这是描述使用乳汁中表达重组人乳铁蛋白(rhLf)的转基因奶牛的实验性乳腺炎模型的第一项研究。本研究的目的是研究牛和重组人乳铁蛋白在实验性大肠杆菌乳腺炎中的乳汁浓度和保护作用。使用 E,在7头初乳的rhLf转基因奶牛和6头正常奶牛的四分之一乳腺中诱发了实验性乳内感染。从临床乳腺炎的奶牛中分离出的大肠杆菌菌株,已知在体外容易感染Lf。在实验期间记录临床体征,确定牛奶中人和牛Lf的浓度以及炎症和细菌计数的指标,并确定血清和牛奶中急性期蛋白和肿瘤坏死因子α的浓度。还测定了血清皮质醇和血液的血液生化参数。在整个实验过程中,转基因奶牛乳中的rhLf表达水平保持恒定(平均值为2.9 mg / ml)。转基因奶牛的牛奶中高Lf浓度不能保护其免受乳房内感染。所有的牛都被感染并发展为临床乳腺炎。与对照相比,rhLf转基因奶牛显示出较轻的全身性体征,并且血清皮质醇和触珠蛋白浓度降低。这可以通过其牛奶中高Lf浓度的脂多糖中和和免疫调节作用来解释。然而,Lf似乎不是用于基因工程以增强奶牛抗乳腺炎的非常有效的蛋白质。

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