Stat5 controls proliferation, differentiation, and survival of mammary alveolar epithelium. Wild-type mammary epithelium differentiates into functional alveoli during pregnancy. When Stat5 deletion occurs prior to pregnancy, the mammary epithelium loses the ability to respond to proliferative signals at the onset of pregnancy; it retains ductal characteristics and fails to acquire a marker indicative of secretory function. When the loss of Stat5 occurs late in pregnancy after mammary epithelia have entered differentiation, differentiation is stalled and premature cell death takes place. (A) The rectangle indicates that Stat5 is expressed throughout mammary gland development, and the red gradient reflects Stat5 activity during pregnancy and lactation. The X refers to the time when Stat5 is inactivated. MC, Stat5 deletion occurs before puberty in Stat5fl/fl/MC mouse. WC, Stat5 deletion takes place during late pregnancy. (B) Schematic presentation of mammary epithelial development in the presence and absence of Stat5. Ducts and alveoli in the upper part depict mammary epithelial development in wild-type mice. Ducts and alveoli in the lower part illustrate the abnormal mammary epithelial development in Stat5fl/fl/MC or Stat5fl/fl/WC mice during pregnancy and lactation. *, milk secretion in the alveoli. The arrow points to the Npt2b localization in the functional alveoli.