Targeting of adult microglia, the brain-resident macrophages
Wong, Ying Xin
Date of Issue2016-08-16
School of Biological Sciences
Singapore Immunology Network
Microglia are known as the resident macrophages in central nervous system (CNS). They play important roles in immune defense, phagocytosis of cellular debris and tissue maintenance in CNS parenchyma. On the other hand, they also contribute to pathological conditions such as neurodegenerative disease and brain injuries. However, the exact mechanisms of their homeostasis are still not well understood and the field is lacking microglia-specific targeting tools to study their function. We have identified Uroplakin 1b (Upk1b), a tetraspanin molecule, to be highly expressed in microglia. Thus, to study the homeostasis of microglia in steady state conditions, we have developed a Uroplakin-1bCre (Upk1bCre) model. When Upk1bCre mouse was crossed with Rosa-LSL-YFP reporter mouse, we observed 80% recombination in the microglia population. Hence, Upk1bCre mouse serves as a useful model for microglia research. Crossing of RosaiDTR/iDTR mouse with Upk1bCre/+ mouse to generate UiDTR model allows microglia-specific depletion upon administration of diphtheria toxin (DT). However, the conditions for the optimal depletion of microglia in this model is still remain elusive. Hence, different concentrations of DT were administered to the mice and depletion profiles of the mice are analyzed, particularly the microglia in brain. It was found that the depletion of microglia is not very significant in this model, but there was depletion of dendritic cells in the spleen and increase of neutrophils in blood.
Final Year Project (FYP)
Nanyang Technological University