- Carries a disruption of the estrogen receptor alpha (Esr1) gene.
- Estrogen receptor beta (Esr2) remains functional.
- Esr1 encodes a 66 kDa protein that binds and mediates the effects of the natural estrogen, 17β-estradiol.
- Male and female homozygotes completely lack functional ERa protein, survive into adulthood, but are infertile, indicating the necessity of estrogen for proper gonadal development in both sexes.
- Female homozygotes have hypoplastic uteri, arrested development of ovarian follicles and rudimentary mammary glands.
- Male homozygotes display atrophy and degeneration of seminiferous tubules, beginning at 10-12 weeks of age, and have decreased longitudinal bone growth and pronounced cortical osteopenia.
- Both males and females display abnormal sexual behavior.
- Homozygotes have been shown to have increases in the number of calcium channels and prolonged QT intervals on EKG examination, indicating a role of estrogen in cardiac disease.
- Heterozygous ERKO-α mice exhibit half-normal levels of functional ERa proteins and are fertile.
- An excellent model to study the role of estrogen receptors in development and maintenance of both reproductive and non-reproductive tissues, bone homeostasis, and the cardiovascular system.
Genetic Background:
C57BL/6 Origin:
The ERKO-α mouse was developed by Kenneth S. Korach of the NIEHS and colleagues in 1993. The model was created by targeting the Esr1 gene in E12TG2a ES cells and injecting the targeted ES cells into C57BL/6J blastocysts. Resultant chimeras were backcrossed to C57BL/6 for ten generations (N10). Taconic received stock from the NIEHS in 1998, and animals were transferred to Taconic for commercial production in 2000. Homozygotes and heterozygotes were generated through HET x HET matings.
Color:
Black Species:
Mouse Initial Publication:
Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. PNAS USA, 90:11162-6.
