Liu X, Robinson G W, Wagner K U, Garrett L, Wynshaw-Boris A, Hennighausen L
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland 20892-1812, USA.
Genes Dev. 1997 Jan 15;11(2):179-86. doi: 10.1101/gad.11.2.179.
Prolactin (PRL) induces mammary gland development (defined as mammopoiesis) and lactogenesis. Binding of PRL to its receptor leads to the phosphorylation and activation of STAT (signal transducers and activators of transcription) proteins, which in turn promote the expression of specific genes. The activity pattern of two STAT proteins, Stat5a and Stat5b, in mammary tissue during pregnancy suggests an active role for these transcription factors in epithelial cell differentiation and milk protein gene expression. To investigate the function of Stat5a in mammopoiesis and lactogenesis we disrupted this gene in mice by gene targeting. Stat5a-deficient mice developed normally and were indistinguishable from hemizygous and wild-type littermates in size, weight, and fertility. However, mammary lobuloalveolar outgrowth during pregnancy was curtailed, and females failed to lactate after parturition because of a failure of terminal differentiation. Although Stat5b has a 96% similarity with Stat5a and a superimposable expression pattern during mammary gland development it failed to counterbalance for the absence of Stat5a. These results document that Stat5a is the principal and an obligate mediator of mammopoietic and lactogenic signaling.
催乳素（PRL）可诱导乳腺发育（定义为乳腺生成）和泌乳。PRL与其受体结合会导致信号转导及转录激活因子（STAT）蛋白磷酸化并激活，进而促进特定基因的表达。妊娠期间乳腺组织中两种STAT蛋白Stat5a和Stat5b的活性模式表明，这些转录因子在上皮细胞分化和乳蛋白基因表达中发挥着积极作用。为了研究Stat5a在乳腺生成和泌乳中的功能，我们通过基因打靶在小鼠中破坏了该基因。Stat5a基因缺陷小鼠发育正常，在体型、体重和生育能力方面与半合子和野生型同窝小鼠没有区别。然而，妊娠期间乳腺小叶腺泡的生长受到抑制，雌性小鼠在分娩后无法泌乳，原因是终末分化失败。尽管Stat5b与Stat5a有96%的相似性，且在乳腺发育过程中表达模式重叠，但它无法弥补Stat5a缺失的影响。这些结果证明，Stat5a是乳腺生成和泌乳信号传导的主要且必不可少的介质。
