Impaired lactation in mice expressing dominant‐negative FADD in mammary epithelium |
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Authors: | Mark Shackleton Lorraine A O'Reilly Kate D Sutherland Mary L Bath Sarah Ellis Andreas Strasser Jane E Visvader Geoffrey J Lindeman |
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Institution: | 1. Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia;2. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;3. Microscopy Research and Imaging Core Facility, The Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia;4. Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, VIC, Australia;5. Department of Medicine, The University of Melbourne, Parkville, VIC, Australia |
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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. Developmental Dynamics 238:1010–1016, 2009. © 2009 Wiley‐Liss, Inc. |
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Keywords: | FADD/Mort lactation apoptosis transgenic mammary gland |
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