Precocious mammary gland development in P-cadherin-deficient mice.
Precocious mammary gland development in P-cadherin-deficient mice.
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P-钙粘蛋白缺陷型小鼠的早熟乳腺发育。
DOI：
10.1083/jcb.139.4.1025
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发表时间：
1997-11-17
期刊：
影响因子：
--
通讯作者：
Hynes RO
中科院分区：
文献类型：
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作者：
Radice GL;Ferreira-Cornwell MC;Robinson SD;Rayburn H;Chodosh LA;Takeichi M;Hynes RO
为了研究 P-钙粘蛋白在体内的功能，我们对小鼠体内编码这种细胞粘附受体的基因进行了突变。与 E- 和 N-钙粘蛋白缺陷小鼠相比，P-钙粘蛋白突变纯合子小鼠是可以存活的。尽管 P-钙粘蛋白在胎盘中表达水平较高，但 P-钙粘蛋白缺失的女性具有生育能力。 P-钙粘蛋白表达局限于乳腺管腔上皮细胞周围的肌上皮细胞。肌上皮作为泌乳所需的收缩组织的作用是明确的，但其在非妊娠动物中的功能尚不清楚。 P-钙粘蛋白突变雌性哺育和维持其后代的能力表明肌上皮的收缩功能不依赖于细胞粘附分子P-钙粘蛋白。处女 P-钙粘蛋白缺失的雌性表现出乳腺的早熟分化。处女体内的肺泡状芽在形态和生物化学（即乳蛋白合成）方面类似于早期怀孕动物的腺体。随着年龄的增长，P-钙粘蛋白突变小鼠的乳腺上皮会出现增生和发育不良。此外，在突变动物的乳腺中观察到异常的淋巴细胞浸润。这些结果表明，P-钙粘蛋白介导的粘附和/或源自细胞间相互作用的信号是乳腺负生长控制的重要决定因素。此外，肌上皮中 P-钙粘蛋白的丢失揭示了该组织在维持下面的分泌性上皮的未分化状态方面的新功能。
To investigate the functions of P-cadherin in vivo, we have mutated the gene encoding this cell adhesion receptor in mice. In contrast to E- and N-cadherin– deficient mice, mice homozygous for the P-cadherin mutation are viable. Although P-cadherin is expressed at high levels in the placenta, P-cadherin–null females are fertile. P-cadherin expression is localized to the myoepithelial cells surrounding the lumenal epithelial cells of the mammary gland. The role of the myoepithelium as a contractile tissue necessary for milk secretion is clear, but its function in the nonpregnant animal is unknown. The ability of the P-cadherin mutant female to nurse and maintain her litter indicates that the contractile function of the myoepithelium is not dependent on the cell adhesion molecule P-cadherin. The virgin P-cadherin–null females display precocious differentiation of the mammary gland. The alveolar-like buds in virgins resemble the glands of an early pregnant animal morphologically and biochemically (i.e., milk protein synthesis). The P-cadherin mutant mice develop hyperplasia and dysplasia of the mammary epithelium with age. In addition, abnormal lymphocyte infiltration was observed in the mammary glands of the mutant animals. These results indicate that P-cadherin–mediated adhesion and/or signals derived from cell–cell interactions are important determinants in negative growth control in the mammary gland. Furthermore, the loss of P-cadherin from the myoepithelium has uncovered a novel function for this tissue in maintaining the undifferentiated state of the underlying secretory epithelium.