Impaired mammary gland development in Cyl-1-/- mice during pregnancy and lactation is epithelial cell autonomous.

摘要

A specific defect of mice lacking cyclin D1 (cyl-1-/-) is impaired development of the mammary gland during pregnancy. It was shown 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. In pregnancy, however, the early proliferative response, characterized by extensive side-branching, still occurred in the absence of cyclin D1. Although prolactin synthesis and release appeared to be normal, lactogenesis was severely compromised. 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 2 receptor isoforms. In cyl-1-/- mammary glands during late pregnancy, there was a decrease in total and phosphorylated Stat5a and delayed onset of milk protein expression. It is concluded that in these mice, there is a delay in mammary development during pregnancy that results in a severely compromised gland at parturition.