An estrogen receptor (ER)α deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo

Monika Jakacka, Masafumi Ito, Fred Martinson, Toshio Ishikawa, Eunjig Lee, J. Larry Jameson

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

We created a nonclassical estrogen receptor (ER) knock-in mouse model by introducing a mutation that selectively eliminates classical ER signaling through estrogen response elements, while preserving the nonclassical ER pathway. Heterozygous nonclassical ER knock-in (NERKI) females are infertile. Their ovaries contain no corpora lutea, reflecting a defect in ovulation, and the stromal cells contain lipid droplets, suggesting altered steroidogenesis. The uteri are enlarged with evidence of cystic endometrial hyperplasia, and the mammary glands are hypoplastic. These phenotypic features indicate differential ER effects on growth and development in various estrogen-responsive tissues. These findings suggest that nonclassical ER signaling pathways play an important physiological role in the development and function of the reproductive system.

Original languageEnglish
Pages (from-to)2188-2201
Number of pages14
JournalMolecular Endocrinology
Volume16
Issue number10
DOIs
Publication statusPublished - 2002 Oct 1

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Estrogen Receptors
Mutation
DNA
Estrogens
Endometrial Hyperplasia
Corpus Luteum
Response Elements
Human Mammary Glands
Stromal Cells
Ovulation
Growth and Development
Uterus
Ovary

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Jakacka, Monika ; Ito, Masafumi ; Martinson, Fred ; Ishikawa, Toshio ; Lee, Eunjig ; Jameson, J. Larry. / An estrogen receptor (ER)α deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. In: Molecular Endocrinology. 2002 ; Vol. 16, No. 10. pp. 2188-2201.
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An estrogen receptor (ER)α deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. / Jakacka, Monika; Ito, Masafumi; Martinson, Fred; Ishikawa, Toshio; Lee, Eunjig; Jameson, J. Larry.

In: Molecular Endocrinology, Vol. 16, No. 10, 01.10.2002, p. 2188-2201.

Research output: Contribution to journalArticle

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