Project description:Experimental Questions: Does knocking out BIN1 have an effect on gene expression in microglia cells? Does BIN1 expression have a different effect in males vs. females?
Project description:Epigenetic alterations has been implicated in the pathology of several neurodegenerative diseases. To investigate the role of microglial Hdac1 and 2 in the pathogenesis of Alzheimer's disease (AD), we created microglia specific compound Hdac1 and Hdac2 knock out mice in 5X FAD background. Genetic ablation of Hdac1 and 2 from microglia reduced amyloid plaque burden and improved spatial learning and memory function. To study how Hdac1 and 2 knock out in microglia alters gene expression profile in 5X FAD mice we carry out microarray analysis using 24-28 weeks animals
Project description:Neuroligin-4 (NL4) loss-of-function mutations are strongly associated with monogenic heritable abnormalities linked with Autism Spectrum Disorder (ASD). NL4 mutation in mice causes ASD related alterations in both synaptic and behavioral phenotypes. Since microglia closely regulate synaptic development and are implicated as key players in ASD development and progression, we here studied microglial properties in the NL4-knock-out (NL4-/-) mouse model. We show that loss of NL4 caused altered behavior and impaired hippocampal gamma oscillations predominantly in male mice. In parallel, microglial density, morphology, and response to injury specifically in the CA3 region of the hippocampus were altered in NL4-/- males only. A transcriptomic and proteomic analysis revealed strong sexual dimorphism on molecular alterations in microglia of NL4-/-. Together, these results indicate that loss of NL4 affects not only neuronal network activity and behavior, but also changes the phenotype of microglia in a sex by genotype interaction .
Project description:We found a kind of GM-CSF producing B cells (BGM) is positively correlated with the pathogenesis of EAE. BGM cell conditional knock-out (CKO) mice showed significant resistance to EAE. To investigate the relationship between BGM cells and microglia and comprehensively evaluate the status of microglia, we obtained microglia from the brain of CKO and control mice at EAE peak stage, extracted microglial RNA, and performed microarray analysis.