Defining vitamin D receptor expression in the brain using a novel VDR(Cre) mouse.
Defining vitamin D receptor expression in the brain using a novel VDR(Cre) mouse.
复制标题
使用新型VDR（Cre）小鼠定义大脑中维生素D受体的表达。
DOI：
10.1002/cne.25100
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Sisley S
中科院分区：
文献类型：
--
作者：
Liu H;He Y;Beck J;da Silva Teixeira S;Harrison K;Xu Y;Sisley S
维生素D的作用与几种由大脑调节的疾病有关，包括肥胖、糖尿病、自闭症和帕金森症。然而，由于相互矛盾的报道，维生素D受体（VDR）在大脑中的位置尚不清楚。我们发现，之前发表的两种在外周组织中具有特异性的抗体在大脑中并不具有特异性。因此，我们在内源性VDR启动子（VDRCre）的控制下，建立了一种新的cre重组酶表达的敲入小鼠。我们证明了VDRCre小鼠大脑中的cre活性（由cre依赖的tdTomato表达报道）与内源性VDR mrna高度重叠。这些表达vdr的细胞在多个大脑区域富集，包括皮层、杏仁核、尾状壳核和下丘脑等。在下丘脑，VDR与加压素、催产素、雌激素受体α和β-内啡肽有不同程度的共定位。我们进一步从功能上验证了我们的模型，证明内源性VDR激动剂1,25-二羟基维生素D激活了室旁下丘脑所有测试的tdTomato+神经元，但对没有tdTomato荧光的神经元没有影响。因此，我们已经生成了一种新的小鼠工具，使我们能够可视化表达vdr的细胞并表征其功能。为了探究维生素D受体在大脑中的解剖结构，我们培育了一种新型的维生素D受体（VDR） VDRCre敲入小鼠。在本文中，我们通过免疫组织化学证明了vdrcres驱动的报告基因表达在整个大脑中与VDR mRNA共定位。此外，我们证明tdTomato（+）神经元对维生素D反应迅速，而tdTomato（−）神经元则没有。
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. We generated a novel vitamin D receptor (VDR) VDRCre knockin mouse for the interrogation of VDR anatomy in the brain. In this paper, we demonstrate through immunohistochemistry that VDRCre-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.
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DOI：
10.1016/j.metabol.2015.12.011
发表时间：
2016-04
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
Saito K;He Y;Yan X;Yang Y;Wang C;Xu P;Hinton AO Jr;Shu G;Yu L;Tong Q;Xu Y
通讯作者：
Xu Y
影响因子：
5.5
作者：
Tamayo, Maria;Manzanares, Esmeralda;Delgado, Carmen
通讯作者：
Delgado, Carmen
影响因子：
4.1
作者：
Cui, Xiaoying;Gooch, Helen;Eyles, Darryl
通讯作者：
Eyles, Darryl
影响因子：
15.9
作者：
Cao, Xuehong;Xu, Pingwen;Xu, Yong
通讯作者：
Xu, Yong
影响因子：
3.7
作者：
Fernandes de Abreu, D A;Eyles, D;Feron, F
通讯作者：
Feron, F