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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:p>Various pathological characteristics of autism spectrum disorder (ASD) stem from abnormalities in brain resident immune cells, specifically microglia, to prune unnecessary synapses or neural connections during early development. Animal models of ASD exhibit an abundance of synapses in different brain regions, which is strongly linked to the appearance of ASD behaviors. Overexpression of CD47 on neurons acts as a \u201cdon\u2019t eat me\u201d signal, safeguarding synapses from inappropriate pruning by microglia. Indeed, CD47 overexpression occurs in 16p11.2 deletion carriers, causing decreased synaptic phagocytosis and the manifestation of ASD characteristics. However, the role of CD47 in synaptic pruning impairment leading to ASD phenotypes in the 16p11.2 deletion mouse model is unclear. Moreover, whether blocking CD47 can alleviate ASD mice\u2019s behavioral deficits remains unknown. Here, we demonstrate a strong link between increased CD47 expression, decreased microglia phagocytosis capacity, and increased impairment in social novelty preference in the 16p11.2 deletion mice. The reduction in microglia phagocytosis caused a rise in excitatory synapses and transmission in the prefrontal cortex of 16p11.2 deletion mice. Importantly, blocking CD47 using a specific CD47 antibody or reducing CD47 expression using a specific short hairpin RNA (shRNA) enhanced the microglia phagocytosis and reduced excitatory transmission. Reduction in CD47 expression improved social novelty preference deficits in 16p11.2 mice. These findings demonstrate that CD47 is associated with the ASD phenotypes in the 16p11.2 deletion mice and could be a promising target for the development of treatment for ASD.<\/jats:p>","DOI":"10.1073\/pnas.2411080122","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T12:13:06Z","timestamp":1744805586000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["The \u201cdon\u2019t eat me\u201d signal CD47 is associated with microglial phagocytosis defects and autism-like behaviors in 16p11.2 deletion mice"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0441-5575","authenticated-orcid":false,"given":"Jun","family":"Ju","sequence":"first","affiliation":[{"name":"Brain Research Centre, Department of Neurobiology, School of Life Sciences, Southern University of Science and Technology","place":["Nanshan District, Shenzhen, Guangdong, People\u2019s 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