Ogg Sherry L, Weldon Anne K, Dobbie Lorraine, Smith Andrew J H, Mather Ian H
Department of Animal and Avian Sciences, University of Maryland, College Park, 20742, USA.
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10084-9. doi: 10.1073/pnas.0402930101. Epub 2004 Jun 28.
Butyrophilin 1a1 (Btn1a1), which is a member of the Ig superfamily, is highly expressed in the lactating mammary gland and is secreted into milk in association with lipid droplets. To determine the potential function of Btn1a1 in milk secretion, we ablated Btn1a1 in mice and analyzed the lactation phenotype of homozygous (Btn1a1(-/-)) animals. Two mutant mouse lines were generated in which expression of Btn1a1 was either disrupted or eliminated, respectively. The regulated secretion of milk-lipid droplets was severely compromised in both mutant mouse lines in comparison to wild-type animals. Large pools of triacylglycerol accumulated in the cytoplasm of secretory cells, and lipid droplets escaped from the apical surface with disrupted outer membranes. Luminal spaces became engorged with unstable lipid droplets, which coalesced to form large aggregates. The amount of lipid (wt/vol) was elevated, on average by 50%, during the first 10 days of lactation, and the diameter of the droplets was up to seven times larger than the normal diameter. In contrast, there was no significant difference between wild-type and null animals in the relative amounts of skim-milk proteins secreted from Golgi-derived secretory vesicles. Approximately half the pups suckling Btn1a1(-/-) animals died within the first 20 days, and weaning weights for the surviving pups were 60-80% of those suckling wild-type mice. Thus, expression of Btn1a1 is essential for the regulated secretion of milk-lipid droplets. We speculate that Btn1a1 functions either as a structural protein or as a signaling receptor by binding to xanthine dehydrogenase/oxidase.
嗜乳脂蛋白1a1（Btn1a1）是免疫球蛋白超家族的成员之一，在泌乳期乳腺中高度表达，并与脂滴一起分泌到乳汁中。为了确定Btn1a1在乳汁分泌中的潜在功能，我们在小鼠中敲除了Btn1a1，并分析了纯合子（Btn1a1(-/-)）动物的泌乳表型。我们构建了两个突变小鼠品系，其中Btn1a1的表达分别被破坏或消除。与野生型动物相比，两个突变小鼠品系中乳汁脂滴的调节分泌均受到严重损害。大量三酰甘油积聚在分泌细胞的细胞质中，脂滴从顶端表面逸出，外膜破裂。管腔空间充满了不稳定的脂滴，这些脂滴聚合并形成大的聚集体。在泌乳的前10天，脂质（重量/体积）的含量平均升高了50%，脂滴直径比正常直径大7倍。相比之下，野生型和基因敲除动物从高尔基体衍生的分泌小泡分泌的脱脂乳蛋白的相对量没有显著差异。大约一半 suckling Btn1a1(-/-) 动物的幼崽在出生后的前20天内死亡，存活幼崽的断奶体重是 suckling 野生型小鼠幼崽的60-80%。因此，Btn1a1的表达对于乳汁脂滴的调节分泌至关重要。我们推测，Btn1a1要么作为一种结构蛋白，要么通过与黄嘌呤脱氢酶/氧化酶结合作为一种信号受体发挥作用。 （注：原文中“suckling”一词在中文语境下较难准确翻译且不影响整体理解，保留英文未译）
