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Science 302 (5650): 1560-1563

Copyright © 2003 by the American Association for the Advancement of Science

Phosphatidylserine Receptor Is Required for Clearance of Apoptotic Cells

Ming O. Li,1,3* Matthew R. Sarkisian,2* Wajahat Z. Mehal,1,4 Pasko Rakic,2 Richard A. Flavell1,3{dagger}

Abstract: Cells undergoing apoptosis during development are removed by phagocytes, but the underlying mechanisms of this process are not fully understood. Phagocytes lacking the phosphatidylserine receptor (PSR) were defective in removing apoptotic cells. Consequently, in PSR-deficient mice, dead cells accumulated in the lung and brain, causing abnormal development and leading to neonatal lethality. A fraction of PSR knockout mice manifested a hyperplasic brain phenotype resembling that of mice deficient in the cell death–associated genes encoding Apaf-1, caspase-3, and caspase-9, which suggests that phagocytes may also be involved in promoting apoptosis. These data demonstrate a critical role for PSR in early stages of mammalian organogenesis and suggest that this receptor may be involved in respiratory distress syndromes and congenital brain malformations.

1 Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
2 Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
4 Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: richard.flavell{at}yale.edu

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