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Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) expressed on astrocytes and myosatellite cells, and recessive mutations in humans result in early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Here we report that Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes ex vivo We also report that cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons and that Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells. In contrast, cells expressing Megf10 with EMARDD mutations have impaired apoptotic cell clearance and impaired binding to C1q. Our studies reveal that Megf10 is a receptor for C1q and identify a novel role for Megf10 in clearance of apoptotic cells in the mammalian developing brain with potential relevance to EMARDD patients and other CNS disorders.
Pubmed ID: 27170117
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Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
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