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Published on: November 15, 2013
Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene
J Xu1, Y Qiu, F J DeMayo
1Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
The in vivo biological function of a steroid receptor coactivator was assessed in mice in which the SRC-1 gene was inactivated by gene targeting. Although in both sexes the homozygous mutants were viable and fertile, target organs such as uterus, prostate, testis, and mammary gland exhibited decreased growth and development in response to steroid hormones. Expression of RNA encoding TIF2, a member of the SRC-1 family, was increased in the SRC-1 null mutant, perhaps compensating partially for the loss of SRC-1 function in target tissues. The results indicate that SRC-1 mediates steroid hormone responses in vivo and that loss of its coactivator function results in partial resistance to hormone.
Insights
Steroid receptor coactivator SRC-1 (steroid receptor coactivator-1) is crucial for steroid hormone responses in mice. Gene inactivation led to reduced organ development and partial hormone resistance, indicating SRC-1
Area of Science:
- Molecular biology
- Endocrinology
- Genetics
Background:
- Steroid receptor coactivators (SRCs) are critical for mediating the effects of steroid hormones.
- SRC-1 is a key member of the SRC family, but its precise in vivo function remains incompletely understood.
Purpose of the Study:
- To investigate the in vivo biological function of SRC-1.
- To determine the consequences of SRC-1 gene inactivation on steroid hormone responses in mice.
Main Methods:
- Gene targeting was used to create SRC-1 null mutant mice.
- Phenotypic analysis of homozygous mutants, including assessment of reproductive organ development and response to steroid hormones.
Main Results:
- Homozygous SRC-1 mutant mice were viable and fertile.
- Target organs (uterus, prostate, testis, mammary gland) showed reduced growth and development in response to steroid hormones.
- Expression of TIF2, a related coactivator, was upregulated in SRC-1 null mutants, suggesting partial compensation.
Conclusions:
- SRC-1 plays a significant role in mediating steroid hormone responses in vivo.
- Loss of SRC-1 function leads to partial resistance to steroid hormones and impaired development of hormone-responsive tissues.
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