SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice.
Prolactin is essential for proliferation and differentiation of the developing mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1 (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1, which were rescued from neonatal death by deletion of the Interferon gamma (IFN gamma) gene. SOCS1(-/-)/IFN gamma(-/-) mice exhibited accelerated lobuloalveolar development in the mammary gland during late pregnancy and precocious lactation. Significantly, the lactogenic defect in prolactin receptor heterozygous females could be rescued by deletion of a single SOCS1 allele. These findings establish a role for SOCS1 as a negative regulator of prolactin signaling and suggest that SOCS1 is required for the prevention of lactation prior to parturition.
Lindeman
G J
GJ
The Walter and Eliza Hall Institute of Medical Research, Bone Marrow Research Laboratories, PO Royal Melbourne Hospital, VIC 3050, Australia.
Wittlin
S
S
Lada
H
H
Naylor
M J
MJ
Santamaria
M
M
Zhang
J G
JG
Starr
R
R
Hilton
D J
DJ
Alexander
W S
WS
Ormandy
C J
CJ
Visvader
J
J
D000483:Alleles; D000818:Animals; D001940:Breast / Q000254:growth & development*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002364:Caseins / Q000096:biosynthesis; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D007774:Lactation / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism; D011247:Pregnancy; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D002364:Caseins; D011981:Receptors, Prolactin; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins