Lactational competence and involution of the mouse mammary gland require plasminogen.
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.
Lund
L R
LR
Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. lund@inet.uni2.dk
Bjørn
S F
SF
Sternlicht
M D
MD
Nielsen
B S
BS
Solberg
H
H
Usher
P A
PA
Osterby
R
R
Christensen
I J
IJ
Stephens
R W
RW
Bugge
T H
TH
Danø
K
K
Werb
Z
Z
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
D005337:Fibrin; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9