Defining VDR expression in the brain using a novel VDRCre mouse

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson’s. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDR Cre ). We demonstrated that the cre activity in the VDR Cre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR mRNAs. These VDR-expressing cells were enriched in multiple brain regions including the cortex, amygdala, caudate putamen, and hypothalamus among others. In the hypothalamus, VDR partially colocalized with vasopressin, oxytocin, estrogen receptor α, and β-endorphin to various degrees. We further functionally validated our model by demonstrating that the endogenous VDR agonist 1,25-dihydroxyvitamin D activated all tested tdTomato+ neurons in the paraventricular hypothalamus but had no effect on neurons without tdTomato fluorescence. Thus, we have generated a new mouse tool that allows us to visualize VDR-expressing cells and to characterize their functions. We generated a novel vitamin D receptor (VDR) VDR Cre knockin mouse for the interrogation of VDR anatomy in the brain. In this paper, we demonstrate through immunohistochemistry that VDR Cre -driven reporter expression colocalizes with VDR mRNA throughout the brain. Additionally, we demonstrate that tdTomato (+) neurons respond rapidly to vitamin D, which does not occur in tdTomato (−) neurons.