Mfge8 Is Critical for Mammary Gland Remodeling during Involution

• DOI: 10.1091/mbc.e05-02-0128
• Publication Date: 2005-09-30T00:24:17Z
• Authors: Kamran Atabai; Rafael Fernandez; Xiaozhu Huang; Iris Ueki; Ahnika Kline; Yong Li; Sepid Sadatmansoori; Christine Smith-S...; Weimin Zhu; Robert Pytela; Zena Werb; Dean Sheppard
• Keywords: Inflammation; Mice, Knockout; Heterozygote; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Homozygote; Cell Culture Techniques; Apoptosis; Epithelial Cells; Milk Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Mammary Glands, Animal; Pregnancy; Antigens, Surface; Animals; Humans; Female

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.