QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 12, 5528-5537, December 2005

This Article Full Text Full Text (PDF) All Versions of this Article: E05-02-0128v1 16/12/5528    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Atabai, K. Articles by Sheppard, D. Search for Related Content PubMed PubMed Citation Articles by Atabai, K. Articles by Sheppard, D.

Mfge8 Is Critical for Mammary Gland Remodeling during Involution

Kamran Atabai ^* , Rafael Fernandez ^* , Xiaozhu Huang ^* , Iris Ueki , Ahnika Kline ^* , Yong Li ^* , Sepid Sadatmansoori ^* , Christine Smith-Steinhart  , Weimin Zhu ^||, Robert Pytela ^||, Zena Werb ^¶, and Dean Sheppard ^* 

^* Lung Biology Center, Cardiovascular Research Institute, University of California–San Francisco, San Francisco, CA 94143; Department of Medicine, University of California–San Francisco, San Francisco, CA 94143; ^¶ Department of Anatomy, University of California–San Francisco, San Francisco, CA 94143; Department of Immunology, University of Colorado Health Science Center, Denver, CO 80206; National Jewish Medical Center and Department of Medicine, University of Colorado Health Science Center, Denver, CO 80206; and ^|| Epitomics, Burlingame, CA 94010

Submitted February 15, 2005; Revised August 17, 2005; Accepted September 15, 2005
Monitoring Editor: M. Bishr Omary

Apoptosis is a critical process in normal mammary gland development and the rapid clearance of apoptotic cells prevents tissue injury associated with the release of intracellular antigens from dying cells. Milk fat globule-EGF-factor 8 (Mfge8) is a milk glycoprotein that is abundantly expressed in the mammary gland epithelium and has been shown to facilitate the clearance of apoptotic lymphocytes by splenic macrophages. We report that mice with disruption of Mfge8 had normal mammary gland development until involution. However, abnormal mammary gland remodeling was observed postlactation in Mfge8 mutant mice. During early involution, Mfge8 mutant mice had increased numbers of apoptotic cells within the mammary gland associated with a delay in alveolar collapse and fat cell repopulation. As involution progressed, Mfge8 mutants developed inflammation as assessed by CD45 and CD11b staining of mammary gland tissue sections. With additional pregnancies, Mfge8 mutant mice developed progressive dilatation of the mammary gland ductal network. These data demonstrate that Mfge8 regulates the clearance of apoptotic epithelial cells during mammary gland involution and that the absence of Mfge8 leads to inflammation and abnormal mammary gland remodeling.

Address correspondence to: Dean Sheppard (dean.sheppard{at}ucsf.edu).

This article has been cited by other articles:

				E. F. Nandrot, M. Anand, D. Almeida, K. Atabai, D. Sheppard, and S. C. Finnemann Essential role for MFG-E8 as ligand for {alpha}vbeta5 integrin in diurnal retinal phagocytosis PNAS, July 17, 2007; 104(29): 12005 - 12010. [Abstract] [Full Text] [PDF]

				M. A. Ensslin and B. D. Shur The EGF repeat and discoidin domain protein, SED1/MFG-E8, is required for mammary gland branching morphogenesis PNAS, February 20, 2007; 104(8): 2715 - 2720. [Abstract] [Full Text] [PDF]