小胶质细胞的吞噬功能不仅参与脑组织稳态还与多种神经疾病的病理发展有关，特异的激活细胞吞噬作用成为治疗该类疾病的思路之一。我们为了寻找特异增强小胶质细胞吞噬作用的因子，对脑表达的17种脂肪因子进行了筛选，首先发现C1QL3可以明显增强小胶质细胞吞噬，而不刺激炎性因子表达。C1QL3是近几年发现的脑组织特异脂肪因子，仅有的几篇文献证实C1QL3与突触密度有关。而C1QL3对小胶质细胞的作用尚无研究。本题拟建立C1QL3敲除和定点转基因大鼠，通过C1QL3功能缺失和功能获得对比，明确C1QL3对小胶质细胞调节作用，阐明C1QL3/BAI3/ELMO1/RAC1通路对小胶质细胞吞噬的调节机制，进而与痴呆（AD）大鼠模型杂交，研究C1QL3对AD病理进程的影响。项目目标不仅建立C1QL3基因修饰和C1QL3基因修饰的AD模型，也有望发现一种针对小胶质细胞吞噬的因子，为AD等的因子治疗提供一种选择。

Phagocytosis of microglia is involved in maintaining central nervous system (CNS ) homeostasis and pathological development of neurological diseases. To induce specific increase of phagocytosis of microglia was a new attempt for therapy of neurological diseases. To find a cytokine being specifically targeted on phagocytosis of microglia, we previously screened 17 brain expressed adipocytokines. C1QL3 was found to increase phagocytosis of rat microglia strongly, but not induced the expression of inflammatory cytokines obviously. C1QL3 is a new brain expressed adipocytokine and only a few papers were published to indicate its function on excitatory synapse density. So far, little is known about the effect of C1QL3 on microglia. In this current project, the C1QL3 knockout rats and C1QL3 transgenic rats at ROSA26 loci are going to be generated and the C1QL3 function on phagocytosis of microglia will be documented comparatively with the C1QL3 loss function rats (ko) and C1QL3 gain function rats(tg) in vivo. The signal pathway of C1QL3/BAI3/ELMO1/RAC1will be also analyzed to indicated if it was necessary on the regulation of microglia phagocytosis. Further, the C1QL3 knockout and transgenic rats will be crossed with Alzheimer disease(AD) rats respectively and illuminated the effect of C1QL3 on the pathological development of AD rats. The arms of this project were not only to generated models of C1QL3 modified rats and C1QL3 modified AD rats, but also to find a adipocytokine being specifically targeted on phagocytosis of microglia, which could offer a potential choice for cytokine therapy of AD.