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Defining vitamin D receptor expression in the brain using a novel VDR Cre mouse
Author(s) -
Liu Hailan,
He Yang,
Beck Jessie,
Silva Teixeira Silvania,
Harrison Keisha,
Xu Yong,
Sisley Stephanie
Publication year - 2021
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.25100
Subject(s) - calcitriol receptor , biology , endocrinology , medicine , hypothalamus , endogeny , receptor , vitamin d and neurology , agonist , microbiology and biotechnology , genetics
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.