Mfge8 is critical for mammary gland remodeling during involution.
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.
Atabai
Kamran
K
Lung Biology Center, Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA 94143, USA.
Fernandez
Rafael
R
Huang
Xiaozhu
X
Ueki
Iris
I
Kline
Ahnika
A
Li
Yong
Y
Sadatmansoori
Sepid
S
Smith-Steinhart
Christine
C
Zhu
Weimin
W
Pytela
Robert
R
Werb
Zena
Z
Sheppard
Dean
D
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis; D018929:Cell Culture Techniques; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007249:Inflammation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000954:Antigens, Surface; C490919:Mfge8 protein, mouse; D008894:Milk Proteins