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Updated: May 30, 2026

Evaluation of Mammary Gland Development and Function in Mouse Models
Published on: July 21, 2011
Repressor of estrogen receptor activity (REA) is essential for mammary gland morphogenesis and functional activities:
Sunghee Park1, Yuechao Zhao, Sangyeon Yoon
1Department of Molecular and Integrative Physiology, University of Illinois, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, Illinois 61801-3704, USA.
Abstract:
Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of the REA gene at different stages of mammary gland development. Notably, we find that heterozygosity and nullizygosity for REA result in very different mammary phenotypes and that REA has essential roles in the distinct morphogenesis and functions of the mammary gland at different stages of development, pregnancy, and lactation. During puberty, mice homozygous null for REA in the mammary gland (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed accelerated mammary ductal elongation, increased numbers of terminal end buds, and up-regulation of amphiregulin, the major paracrine mediator of estrogen-induced ductal morphogenesis. During pregnancy and lactation, mice with homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein-Cre) showed a loss of lobuloalveolar structures and increased apoptosis of mammary alveolar epithelium, leading to impaired milk production and significant reduction in growth of their offspring, whereas body weights of the offspring nursed by females heterozygous for REA were slightly greater than those of control mice. Our findings reveal that REA is essential for mammary gland development and has a gene dosage-dependent role in the regulation of stage-specific physiological functions of the mammary gland.
Insights
The repressor of estrogen receptor activity (REA) is crucial for mammary gland development. Its loss impacts ductal elongation, lobuloalveolar structures, and milk production in a gene dosage-dependent manner.
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Biology
Background:
- Estrogen receptor (ER) signaling is vital for mammary gland development and breast cancer.
- ER activity relies on coregulator proteins, including repressor of ER activity (REA).
- Understanding REA's role is key to deciphering ER-mediated mammary gland functions.
Purpose of the Study:
- To investigate the functional consequences of REA gene dosage on mammary gland development and function.
- To determine REA's role during different physiological stages: puberty, pregnancy, and lactation.
Main Methods:
- Conditional gene deletion of REA alleles in mouse mammary glands.
- Utilizing PRcre and WAP-Cre mouse lines to target REA deletion at specific developmental stages.
- Phenotypic analysis of mammary gland morphology, ductal elongation, and offspring growth.
Main Results:
- Homozygous REA deletion (nullizygosity) severely impaired pubertal mammary ductal elongation and morphogenesis.
- Heterozygous REA deficiency accelerated ductal elongation and increased terminal end buds during puberty.
- Homozygous REA deletion during pregnancy/lactation led to loss of lobuloalveolar structures, increased apoptosis, impaired milk production, and reduced offspring growth.
- Heterozygous REA deficiency during pregnancy/lactation resulted in slightly increased offspring body weights.
Conclusions:
- REA plays essential, gene dosage-dependent roles in mammary gland development and function.
- REA is critical for stage-specific mammary gland morphogenesis and physiological processes like lactation.
- Differential effects of REA heterozygosity and nullizygosity highlight its complex regulatory functions.
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