Defining VDR Expression in the Brain Using a Novel VDRCre Mouse

Authors

Hailan Liu
Yang He
Jessie Beck
Silvania da Silva Teixeira
Keisha Harrison
Yong Xu
Stephanie Sisley

Publication Date

6-1-2021

Journal

Journal of Comparative Neurology

DOI

10.1002/cne.25100

PMID

33368246

PMCID

PMC8053677

PubMedCentral® Posted Date

6-1-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Brain, Brain Chemistry, Female, Gene Expression, Male, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Knockout, Mice, Transgenic, Pregnancy, Receptors, Calcitriol, Mutant mouse strain, Brain, Vitamin D receptor, Immunohistochemistry, RRID:AB_628040, RRID:AB_632069, RRID:AB_141637, RRID:AB_2832252, RRID:AB_2715552, RRID:AB_2157629, RRID:AB_310305, RRID:AB_2314007

Abstract

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 (VDRCre). We demonstrated that the cre activity in the VDRCre 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.