摘要：SummaryTheSUSD4(Sushi domain-containing protein 4) gene encodes a complement inhibitor that is frequently deleted in 1q41q42 microdeletion syndrome, a multisystem congenital disorder that includes neurodevelopmental abnormalities. To understand SUSD4's role in the mammalian nervous system, we analyzedSusd4knockout (KO) mice.Susd4KO mice exhibited significant defects in motor performance and significantly higher levels of anxiety-like behaviors.Susd4KO brain had abnormal “hairy” basket cells surrounding Purkinje neurons within the cerebellum and significantly reduced dendritic spine density in hippocampal pyramidal neurons. Neurons and oligodendrocyte lineage cells of wild-type mice were found to expressSusd4mRNA. Protein expression of the complement component C1q was increased in the brains ofSusd4KO mice. Our data indicate that SUSD4 plays an important role in neuronal functions, possibly via the complement pathway, and thatSUSD4deletion may contribute to the nervous system abnormalities in patients with 1q41q42 deletions.Graphical AbstractDisplay OmittedHighlights•Susd4is expressed in neurons and oligodendrocyte lineage cells•Susd4knockout mice have abnormal hippocampal and cerebellar neuronal morphologies•Susd4knockout mice exhibit anxiety-like behaviors and impaired motor function•Susd4knockout mice have elevated brain levels of the complement component C1qBehavioral Neuroscience; Cellular Neuroscience; Components of the Immune System; Neuroscience
