PMID- 8491177
OWN - NLM
STAT- MEDLINE
DCOM- 19930611
LR  - 20220511
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 12
IP  - 5
DP  - 1993 May
TI  - Targeting expression of a transforming growth factor beta 1 transgene to the 
      pregnant mammary gland inhibits alveolar development and lactation.
PG  - 1835-45
AB  - Transforming growth factor-beta 1 (TGF-beta 1) possesses highly potent, diverse 
      and often opposing cell-specific activities, and has been implicated in the 
      regulation of a variety of physiologic and developmental processes. To determine 
      the effects of in vivo overexpression of TGF-beta 1 on mammary gland function, 
      transgenic mice were generated harboring a fusion gene consisting of the porcine 
      TGF-beta 1 cDNA placed under the control of regulatory elements of the 
      pregnancy-responsive mouse whey-acidic protein (WAP) gene. Females from two of 
      four transgenic lines were unable to lactate due to inhibition of the formation 
      of lobuloalveolar structures and suppression of production of endogenous milk 
      protein. In contrast, ductal development of the mammary glands was not overtly 
      impaired. There was a complete concordance in transgenic mice between 
      manifestation of the lactation-deficient phenotype and expression of RNA from the 
      WAP/TGF-beta 1 transgene, which was present at low levels in the virgin gland, 
      but was greatly induced at mid-pregnancy. TGF-beta 1 was localized to numerous 
      alveoli and to the periductal extracellular matrix in the mammary gland of 
      transgenic females late in pregnancy by immunohistochemical analysis. Glands 
      reconstituted from cultured transgenic mammary epithelial cells duplicated the 
      inhibition of lobuloalveolar development observed in situ in the mammary glands 
      of pregnant transgenic mice. Results from this transgenic model strongly support 
      the hypothesis that TGF-beta 1 plays an important in vivo role in regulating the 
      development and function of the mammary gland.
FAU - Jhappan, C
AU  - Jhappan C
AD  - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
FAU - Geiser, A G
AU  - Geiser AG
FAU - Kordon, E C
AU  - Kordon EC
FAU - Bagheri, D
AU  - Bagheri D
FAU - Hennighausen, L
AU  - Hennighausen L
FAU - Roberts, A B
AU  - Roberts AB
FAU - Smith, G H
AU  - Smith GH
FAU - Merlino, G
AU  - Merlino G
LA  - eng
PT  - Journal Article
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Milk Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (whey acidic proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
GS  - TGF-&bgr;-1
GS  - WAP
MH  - Animals
MH  - Cell Differentiation
MH  - DNA
MH  - Female
MH  - Gene Expression
MH  - Immunohistochemistry
MH  - Lactation/genetics/*physiology
MH  - Male
MH  - Mammary Glands, Animal/cytology/metabolism/*physiology
MH  - Mice
MH  - Mice, Transgenic
MH  - Milk Proteins/genetics
MH  - Pregnancy
MH  - Swine
MH  - Transforming Growth Factor beta/genetics/*physiology
PMC - PMC413404
EDAT- 1993/05/01 00:00
MHDA- 1993/05/01 00:01
PMCR- 1994/05/01
CRDT- 1993/05/01 00:00
PHST- 1993/05/01 00:00 [pubmed]
PHST- 1993/05/01 00:01 [medline]
PHST- 1993/05/01 00:00 [entrez]
PHST- 1994/05/01 00:00 [pmc-release]
AID - 10.1002/j.1460-2075.1993.tb05832.x [doi]
PST - ppublish
SO  - EMBO J. 1993 May;12(5):1835-45. doi: 10.1002/j.1460-2075.1993.tb05832.x.