Urokinase-type plasminogen activator expression is induced in the mouse mammary gland during development and post-lactational involution. We now show that primiparous plasminogen-deficient (Plg(−/−)) mice have seriously compromised mammary gland development and involution. All mammary glands were underdeveloped and one-quarter of the mice failed to lactate. Although the glands from lactating Plg(−/−) mice were initially smaller, they failed to involute after weaning, and in most cases they failed to support a second litter. Alveolar regression was markedly reduced and a fibrotic stroma accumulated in Plg(−/−) mice. Nevertheless, urokinase and matrix metalloproteinases (MMPs) were upregulated normally in involuting glands of Plg(−/−) mice, and fibrin did not accumulate in the glands. Heterozygous Plg(+/−) mice exhibited haploinsufficiency, with a definite, but less severe mammary phenotype. These data demonstrate a critical, dose-dependent requirement for Plg in lactational differentiation and mammary gland remodeling during involution.
Lactational competence and involution of the mouse mammary gland require plasminogen
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L.R. Lund, S.F. Bjorn, M.D. Sternlicht, B.S. Nielsen, H. Solberg, P.A. Usher, R. Osterby, I.J. Christensen, R.W. Stephens, T.H. Bugge, K. Dano, Z. Werb; Lactational competence and involution of the mouse mammary gland require plasminogen. Development 15 October 2000; 127 (20): 4481–4492. doi: https://doi.org/10.1242/dev.127.20.4481
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