Coester Bernd, Foll Christelle Le, Lutz Thomas A
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich (UZH), 8057 Zurich, Switzerland.
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich (UZH), 8057 Zurich, Switzerland.
Physiol Behav. 2020 Sep 1;223:112992. doi: 10.1016/j.physbeh.2020.112992. Epub 2020 Jun 1.
The area postrema (AP), located in the caudal hindbrain, is one of the primary binding sites for the endocrine satiation hormone amylin. Amylin is co-secreted with insulin from pancreatic ß-cells and binds to heterodimeric receptors that consist of a calcitonin core receptor (CTR) paired with receptor-activity modifying protein (RAMP) 1 or 3. In this study, we aim to validate a CTR-floxed (CTR) mouse model for the functional and site-specific depletion of amylin/CTR signaling in the AP and the nucleus tractus solitarius (NTS). CTR mice were injected in the NTS with adeno-associated virus (AAV) containing a green fluorescent protein tag (GFP) and Cre recombinase to create a locally restricted knockout of CTR in the caudal hindbrain. KO mice showed a lack of c-Fos expression, a marker for neuronal activation, in the AP, NTS and LPBN after amylin injection. The effect of amylin and salmon calcitonin (sCT), an amylin receptor agonist, on food intake was blunted in KO mice, confirming a functional reduction of amylin signaling in the hindbrain.
最后区（AP）位于后脑尾部，是内分泌饱腹感激素胰淀素的主要结合位点之一。胰淀素与胰岛素共同从胰腺β细胞分泌，并与由降钙素核心受体（CTR）与受体活性修饰蛋白（RAMP）1或3配对组成的异二聚体受体结合。在本研究中，我们旨在验证一种CTR基因敲除（CTR）小鼠模型，用于在最后区和孤束核（NTS）中功能性和位点特异性地消除胰淀素/CTR信号传导。向CTR小鼠的孤束核注射含有绿色荧光蛋白标签（GFP）和Cre重组酶的腺相关病毒（AAV），以在后脑尾部产生局部受限的CTR基因敲除。基因敲除小鼠在注射胰淀素后，最后区、孤束核和外侧脑桥臂旁核中缺乏作为神经元激活标志物的c-Fos表达。基因敲除小鼠中，胰淀素和鲑鱼降钙素（sCT，一种胰淀素受体激动剂）对食物摄入的影响减弱，证实了后脑胰淀素信号传导的功能降低。
