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Open Access Highly Accessed Research article

The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

Jens Böse1, Achim D Gruber2, Laura Helming1, Stefanie Schiebe1, Ivonne Wegener1, Martin Hafner3, Marianne Beales4, Frank Köntgen4 and Andreas Lengeling1*

Author Affiliations

1 Junior Research Group Infection Genetics, German Research Center for Biotechnology (GBF), Mascheroder Weg 1, 38124 Braunschweig, Germany

2 Department of Pathology, School of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany

3 Department of Experimental Immunology, German Research Center for Biotechnology (GBF), Mascheroder Weg 1, 38124 Braunschweig, Germany

4 Ozgene Pty. Ltd., Canning Vale, WA 6970, Australia

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Journal of Biology 2004, 3:15  doi:10.1186/jbiol10

Published: 23 August 2004

Abstract

Background

Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr) on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse.

Results

Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide.

Conclusion

Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.