Lactation defect in mice lacking the helix-loop-helix inhibitor Id2

Id proteins are thought to be negative regulators of cell differentiation a nd positive regulators of cell proliferation. Mammary glands of ITd2(-/-) f emale mice reveal severely impaired lobulo-alveolar development during preg nancy. Id2(-/-) mammary epithelia show no precocious maturation, but instea d exhibit intrinsic defects in both cell proliferation and cell survival, i mplying that the role of Id2 in pregnant mammary epithelia is mainly stimul ation of cell proliferation and support of cell viability. Expression studi es of genes required for mammary gland development suggest Id2 to be a down stream or parallel factor of these genes. A decrease in the DNA binding act ivity of Stat5 was also observed in Id2(-/-) mammary glands at 7 days post- coitus. Our results indicate an indispensable role of Id2 in pregnant mamma ry glands.