Project Summary
Complement component 3 (C3) helps mediate synaptic elimination during the development of the mouse brain and is upregulated in Alzheimer’s disease (AD), a condition in which synaptic loss is an early event. Recently, we reported that aged C3 knockout mice were protected against age- and brain region-dependent synapse and neuron loss, and had superior cognitive performance compared to age-matched normal mice (Shi et al, J Neurosci, 2015). Therefore, we recently generated two novel C3 conditional knockout mouse models in which C3 expression can be “shut off” at any age by tamoxifen injection, or deleted in all myeloid immune cells (only) throughout life, to distinguish C3’s effects on brain development versus aging and neurodegeneration. I will use high-resolution confocal microscopy to quantify structural synapses and novel microglia-specific antibodies to determine the effects of post-development global C3 deletion or myeloid-specific C3 deletion in these newly generated mice at different ages. In addition, I will crossbreed one of our C3 cKO mouse lines with AD mice to generate the first-ever, AD mouse model in which C3 expression can be deleted at any age.
