Impaired mammary gland development in Cyl-1-/- mice during pregnancy and lactation is epithelial cell autonomous
Impaired mammary gland development in Cyl-1-/- mice during pregnancy and lactation is epithelial cell autonomous
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DOI：
10.1006/dbio.1999.9329
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发表时间：
1999-08-01
影响因子：
2.7
通讯作者：
Dickson, C
中科院分区：
文献类型：
--
作者：
Fantl, V;Edwards, PAW;Dickson, C
缺乏细胞周期蛋白D1（Cyl-1（-/-））的小鼠的一个特定缺陷是妊娠期间乳腺发育受损。在这里，我们表明，当从Cyl-1（-/-）乳腺组织移植到空的野生型小鼠乳腺脂肪垫，异常表型保持，这表明它是上皮细胞自主。然而，在妊娠早期增殖反应，其特征是广泛的侧支，仍然发生在细胞周期蛋白D1的情况下。然而，由于伴随肺泡的形成显著减少，该反应是非典型的。这种肺泡发育的减少和延迟在整个妊娠期间持续存在。此外，虽然催乳素的合成和释放似乎是正常的，但泌乳严重受损。与大量侧支的出现一致，孕激素受体表达在妊娠Cyl-1（-/-）小鼠的乳腺组织中很容易检测到，尽管两种（A和B）受体亚型的比例有显著变化。在Cyl-1（-/-）乳腺在怀孕后期有一个总的和磷酸化的Stat 5a的丰度减少，以及延迟发病和大量减少的牛奶蛋白表达。生化分析表明，在怀孕期间，乳腺的生长和分化有一个累积的延迟，导致在一个严重受损的腺体时，在分娩时，进一步的发展是由激素环境的突然变化削减。(C)北京：科学出版社.
A specific defect of mice lacking cyclin D1 (Cyl-1(-/-)) is impaired development of the mammary gland during pregnancy. Here we show that when tissue from Cyl-1(-/-) mammary gland was transplanted into empty mammary fat pad of wild-type mice, the abnormal phenotype was maintained, indicating that it is epithelial cell autonomous. Nevertheless, in pregnancy the early proliferative response, which is characterized by extensive side branching, still occurs in the absence of cyclin D1. However, the response is atypical due to a marked reduction in the formation of accompanying alveoli. This reduction and delay in alveolar development persists throughout pregnancy. Moreover, although prolactin synthesis and release appear to be normal, lactogenesis is severely compromised. Consistent with the appearance of numerous side branches, progesterone receptor expression was readily detected in the mammary tissue of pregnant Cyl-1(-/-) mice, although there was a significant change in the ratio of the two (A and B) receptor isoforms. In Cyl-1(-/-) mammary glands during late pregnancy there was a decrease in the abundance of total and phosphorylated Stat5a, as well as delayed onset and substantial diminution of milk protein expression. The biochemical analysis suggests that there is a cumulative delay in growth and differentiation of the mammary gland during pregnancy that results in a severely compromised gland when, at parturition, further development is curtailed by the abrupt change in hormonal milieu. (C) 1999 Academic Press.