Underdeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein gene, which is a direct target of estrogen receptor alpha.
The biological roles of estrogen-responsive finger protein (efp) in vivo were evaluated in mice carrying a loss-of-function mutation in efp by gene-targeted mutagenesis. Although efp homozygous mice were viable and fertile in both sexes, the uterus that expressed abundant estrogen receptor alpha exhibited significant underdevelopment. When the ovariectomized homozygotes were subjected to 17beta-estradiol treatment, they showed remarkably attenuated responses to estrogen, as exemplified by decreased interstitial water imbibition and retarded endometrial cell increase, at least, attributable to the lower ratio of G1 to S-phase progression in epithelial cells. These results suggest that efp is essential for the normal estrogen-induced cell proliferation and uterine swelling as one of the direct targets of estrogen receptor alpha.
Orimo
A
A
Department of Biochemistry, Saitama Medical School, 38 Moro-Hongo, Moroyama-machi, Iruma-gun, Saitama, 350-0451, Japan.
Inoue
S
S
Minowa
O
O
Tominaga
N
N
Tomioka
Y
Y
Sato
M
M
Kuno
J
J
Hiroi
H
H
Shimizu
Y
Y
Suzuki
M
M
Noda
T
T
Muramatsu
M
M
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015723:Gene Library; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008957:Models, Genetic; D010641:Phenotype; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014599:Uterus / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology*
D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D014157:Transcription Factors; C490034:Trim25 protein, mouse; D000070584:Tripartite Motif Proteins; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; D001973:Bromodeoxyuridine