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Updated: Jun 2, 2026
Evaluation of Mammary Gland Development and Function in Mouse Models
Published on: July 21, 2011
Lactation defect in a widely used MMTV-Cre transgenic line of mice
Taichang Yuan1, Yongping Wang, Lily Pao
1Department of Pathology, University of Colorado School of Medicine, University of Colorado, Aurora, Colorado, United States of America.
Background:
MMTV-Cre mouse lines have played important roles in our understanding about the functions of numerous genes in mouse mammary epithelial cells during mammary gland development and tumorigenesis. However, numerous studies have not included MMTV-Cre mice as controls, and many investigators have not indicated which of the different MMTV-Cre founder lines were used in their studies. Here, we describe a lactation defect that severely limits the use of one of the most commonly used MMTV-Cre founder lines.
Methodology/Principal Findings:
To explore the role of protein tyrosine phosphatase Shp1 in mammary gland development, mice bearing the floxed Shp1 gene were crossed with MMTV-Cre mice and mammary gland development was examined by histological and biochemical techniques, while lactation competency was assessed by monitoring pup growth. Surprisingly, both the Shp1fl/+;MMTV-Cre and MMTV-Cre female mice displayed a severe lactation defect when compared to the Shp1 fl/+ control mice. Histological and biochemical analyses reveal that female mice expressing the MMTV-Cre transgene, either alone or in combination with floxed genes, exhibit defects in lobuloalveolar expansion, presence of large cytoplasmic lipid droplets in luminal alveolar epithelial cells postpartum, and precocious induction of involution. Using a PCR-based genotyping method, the three different founder lines can be distinguished, and we determined that the MMTV-Cre line A, the most widely used MMTV-Cre founder line, exhibits a profound lactation defect that limits its use in studies on mammary gland development.
Conclusions/Significance:
The identification of a lactation defect in the MMTV-Cre line A mice indicates that investigators must use MMTV-Cre alone mice as control in studies that utilize Cre recombinase to excise genes of interest from mammary epithelial cells. Our results also suggest that previous results obtained in studies using the MMTV-Cre line A line should be re-evaluated if the controls did not include mice expressing only Cre recombinase.
Insights
MMTV-Cre line A mice exhibit a severe lactation defect, impacting mammary gland development and tumorigenesis studies. Researchers must use MMTV-Cre alone mice as controls to ensure accurate gene function analysis in mammary epithelial cells.
Area of Science:
- Mammary gland biology
- Mouse models in genetics
- Gene function studies
Background:
- MMTV-Cre mouse lines are crucial for studying gene function in mammary epithelial cells.
- Inconsistent use of MMTV-Cre controls and unspecified founder lines complicate research.
- A significant lactation defect in a common MMTV-Cre founder line is identified.
Purpose of the Study:
- To investigate the role of Shp1 in mammary gland development using MMTV-Cre mice.
- To characterize the lactation defect observed in MMTV-Cre mice.
- To establish appropriate control groups for studies using MMTV-Cre technology.
Main Methods:
- Crossing MMTV-Cre mice with floxed Shp1 mice.
- Histological and biochemical analyses of mammary gland development.
- Assessment of lactation competency by monitoring pup growth.
- PCR-based genotyping to distinguish MMTV-Cre founder lines.
Main Results:
- Both MMTV-Cre and Shp1fl/+;MMTV-Cre female mice showed severe lactation defects.
- MMTV-Cre transgene expression alone caused defects in lobuloalveolar expansion and induced precocious involution.
- Line A, a widely used MMTV-Cre founder line, exhibits a profound lactation defect.
- Defects included large cytoplasmic lipid droplets in postpartum luminal alveolar epithelial cells.
Conclusions:
- MMTV-Cre line A possesses a lactation defect, limiting its utility.
- Studies using MMTV-Cre line A require MMTV-Cre alone mice as controls.
- Previous findings using MMTV-Cre line A may need re-evaluation if proper controls were not used.
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