TY - JOUR
T1 - Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility
AU - Cui, Yongzhi
AU - Miyoshi, Keiko
AU - Claudio, Estefania
AU - Siebenlist, Ulrich K.
AU - Gonzalez, Frank J.
AU - Flaws, Jodi
AU - Wagner, Kay Uwe
AU - Hennighausen, Lothar
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/5/17
Y1 - 2002/5/17
N2 - The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B-and T-cells. PPARγ has an anti-proliferative effect in pre-adipocytes and mammary epithelial cells, and treatment with its ligands reduced the progression of carcinogen-induced mammary tumors in mice. Because PPARγ-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARγ is required for the establishment and physiology of different cell types, a cellspecific deletion of the gene was carried out in mice using the Cre-loxP recombination system. We deleted the PPARγ gene in mammary epithelium using WAP-Cre transgenic mice and in epithelial cells, B- and T-cells, and ovary cells using MMTV-Cre mice. The presence of PPARγ was not required for functional development of the mammary gland during pregnancy and for the establishment of B- and T-cells. In addition, no increase in mammary tumors was observed. However, loss of the PPARγ gene in oocytes and granulosa cells resulted in impaired fertility. These mice have normal populations of follicles, they ovulate and develop corpora lutea. Although progesterone levels are decreased and implantation rates are reduced, the exact cause of the impaired fertility remains to be determined.
AB - The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B-and T-cells. PPARγ has an anti-proliferative effect in pre-adipocytes and mammary epithelial cells, and treatment with its ligands reduced the progression of carcinogen-induced mammary tumors in mice. Because PPARγ-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARγ is required for the establishment and physiology of different cell types, a cellspecific deletion of the gene was carried out in mice using the Cre-loxP recombination system. We deleted the PPARγ gene in mammary epithelium using WAP-Cre transgenic mice and in epithelial cells, B- and T-cells, and ovary cells using MMTV-Cre mice. The presence of PPARγ was not required for functional development of the mammary gland during pregnancy and for the establishment of B- and T-cells. In addition, no increase in mammary tumors was observed. However, loss of the PPARγ gene in oocytes and granulosa cells resulted in impaired fertility. These mice have normal populations of follicles, they ovulate and develop corpora lutea. Although progesterone levels are decreased and implantation rates are reduced, the exact cause of the impaired fertility remains to be determined.
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U2 - 10.1074/jbc.M200186200
DO - 10.1074/jbc.M200186200
M3 - Article
C2 - 11884400
AN - SCOPUS:0037124098
VL - 277
SP - 17830
EP - 17835
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 20
ER -