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Updated: Jun 24, 2026
Mouse Mammary Epithelial Cells form Mammospheres During Lactogenic Differentiation
Published on: October 6, 2009
Impaired lactation in mice expressing dominant-negative FADD in mammary epithelium
Mark Shackleton1, Lorraine A O'Reilly, Kate D Sutherland
1Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Abstract:
The Fas-associated death domain (FADD/Mort1) adaptor protein was originally identified as a key mediator of apoptosis, although pleiotropic functions for FADD have also been reported. FADD-mediated tumoricidal effects have been described in breast cancer cells; however, its physiological role in normal mammary gland epithelium is not well understood. To determine the role of FADD signaling during mammary gland development, we generated transgenic mice overexpressing dominant-negative FADD (DN-FADD) in mammary epithelium, using the steroid responsive mouse mammary tumor virus promoter. Transgenic mice exhibited a perturbation in lactation resulting in impaired milk production and pup growth retardation. Reduced expansion of alveoli was evident during early lactation with extensive shedding of luminal alveolar cells. Significantly more TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling)-positive cells were present at this time point and a subsequent increase in bromodeoxyuridine-positive cells was observed. These findings suggest a role for FADD in maintaining the survival of mammary secretory alveolar cells after the establishment of lactation.
Insights
Fas-associated death domain (FADD) protein is crucial for mammary gland development. Inhibiting FADD in mice impaired lactation and caused alveolar cell loss, indicating FADD
Area of Science:
- Cell biology
- Developmental biology
- Molecular biology
Background:
- The Fas-associated death domain (FADD) adaptor protein is known to mediate apoptosis and has roles in tumor suppression.
- While FADD's role in cancer cells is studied, its function in normal mammary gland development remains unclear.
Purpose of the Study:
- To investigate the physiological role of FADD signaling in normal mammary gland development and lactation.
- To determine if FADD influences the survival of mammary secretory alveolar cells.
Main Methods:
- Generated transgenic mice overexpressing dominant-negative FADD (DN-FADD) in mammary epithelium using a mouse mammary tumor virus promoter.
- Analyzed mammary gland development, lactation efficiency, and cell survival markers (TUNEL, bromodeoxyuridine) during lactation.
Main Results:
- Transgenic mice showed impaired lactation, reduced milk production, and slower pup growth.
- Mammary glands exhibited reduced alveolar expansion and significant shedding of luminal alveolar cells during early lactation.
- Increased TUNEL-positive cells and subsequent increase in bromodeoxyuridine-positive cells indicated elevated cell death and proliferation.
Conclusions:
- FADD signaling is essential for maintaining the survival of mammary secretory alveolar cells post-lactation establishment.
- Dysregulation of FADD impacts mammary gland function, particularly during the critical lactation period.
