title: Lactational competence and involution of the mouse mammary gland require plasminogen.
abstract: 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.
authors.affiliation: Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. lund@inet.uni2.dk
authors.forename: L R
authors.initials: LR
authors.lastname: Lund
authors.forename: S F
authors.initials: SF
authors.lastname: Bjørn
authors.forename: M D
authors.initials: MD
authors.lastname: Sternlicht
authors.forename: B S
authors.initials: BS
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Solberg
authors.forename: P A
authors.initials: PA
authors.lastname: Usher
authors.forename: R
authors.initials: R
authors.lastname: Osterby
authors.forename: I J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: R W
authors.initials: RW
authors.lastname: Stephens
authors.forename: T H
authors.initials: TH
authors.lastname: Bugge
authors.forename: K
authors.initials: K
authors.lastname: Danø
authors.forename: Z
authors.initials: Z
authors.lastname: Werb
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000502:physiology; D005337:Fibrin / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010958:Plasminogen / Q000172:deficiency* / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D005337:Fibrin; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9