Stinnakre M G, Vilotte J L, Soulier S, Mercier J C
Laboratoire de Génétique Biochimique et de Cytogénétique, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6544-8. doi: 10.1073/pnas.91.14.6544.
alpha-Lactalbumin is an abundant milk-specific calcium metalloprotein which has an evolutionary relationship to lysozyme. It modifies the substrate specificity of a Golgi galactosyltransferase by forming the lactose synthetase binary complex. Lactose, together with other sugars and diffusible ions, is responsible for the osmotic pressure of milk. To assess the involvement of alpha-lactalbumin in lactogenesis, alpha-lactalbumin-deficient mice were created by disrupting the gene by homologous recombination in embryonic stem cells. Homozygous mutant mice are viable and fertile but females cannot feed their offspring. They produce a highly viscous milk that pups appear to be unable to remove from the mammary gland. This milk is rich in fat and protein and is devoid of alpha-lactalbumin and lactose. The phenotype of heterozygous mice was found to be intermediate, with a 40% decrease in alpha-lactalbumin but only a 10-20% decrease in the lactose content of their milk compared with wild-type animals. These results emphasize the key function of alpha-lactalbumin in lactogenesis and open new opportunities to manipulate milk composition.
α-乳白蛋白是一种丰富的乳特异性钙金属蛋白，与溶菌酶具有进化关系。它通过形成乳糖合酶二元复合物来改变高尔基体半乳糖基转移酶的底物特异性。乳糖与其他糖类和可扩散离子一起，决定了乳汁的渗透压。为了评估α-乳白蛋白在泌乳过程中的作用，通过在胚胎干细胞中进行同源重组破坏该基因，培育出了α-乳白蛋白缺陷型小鼠。纯合突变小鼠能够存活且可育，但雌性小鼠无法哺育后代。它们分泌的乳汁高度黏稠，幼崽似乎无法从乳腺中吸出。这种乳汁富含脂肪和蛋白质，不含α-乳白蛋白和乳糖。杂合小鼠的表型介于两者之间，与野生型动物相比，其α-乳白蛋白含量降低了40%，但其乳汁中的乳糖含量仅降低了10 - 20%。这些结果强调了α-乳白蛋白在泌乳过程中的关键作用，并为调控乳汁成分开辟了新的途径。
