1777-P: Defining VDR Expression in the Brain Using a Novel VDR-Cre Mouse Line

The central nervous system mediates the effects of vitamin D on energy and glucose balance, but the distribution of vitamin D receptor (VDR) in the brain is not clear due to the lack of reliable antibodies. Here, we generated a knock-in VDR-Cre mouse line, in which cre recombinase activity is driven by the endogenous VDR promoter. By mating VDR-Cre mice with TdTomato reporter mice, we found that VDR-expressing neurons are located in multiple brain regions, including the cortex, hypothalamus, amygdala and caudate putamen. We further verified the specificity of our model through single cell RT-PCR, which showed significantly higher vdr expression in tomato⁺ cells. More importantly, our in vitro electrophysiological study revealed that vitamin D can selectively activate tomato⁺ neurons, without affecting tomato^- neurons. By using immunofluorescence staining, we found a small portion of VDR positive neurons also express oxytocin, ß-endorphin, ERα or serotonin. Interestingly, in the ventromedial hypothalamus, ERα co-localized with only 1% tomato⁺ neurons in males but 8% tomato⁺ neurons in females. Taken together, we created and validated a novel VDR-Cre mouse line, which provides a useful tool for future studies to investigate the functions of VDR in the brain.