Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter
Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter
复制标题
DOI：
10.1523/jneurosci.23-18-07143.2003
复制
发表时间：
2003-08-06
影响因子：
5.3
通讯作者：
Elmquist, JK
中科院分区：
文献类型：
--
作者：
Liu, HY;Kishi, T;Elmquist, JK
黑素皮质素-4受体(MC4-R)是能量稳态的重要调节因子，有证据表明MC4-R表达的神经元是瘦素作用的下游靶点。MC4-R在中枢神经系统中广泛表达，对其在大鼠体内的分布进行了最广泛的分析。然而，关于MC4-R表达神经元的化学特征知之甚少。中枢黑素皮质素在突触前或突触后对MC4受体的作用程度也是未知的。为了解决这些问题，我们使用改良的细菌人工染色体，在MC4-R启动子的控制下，建立了表达绿色荧光蛋白(GFP)的转基因小鼠系。我们已经证实，在野生型小鼠中，GFP产生细胞的中枢神经系统分布与MC4-R mRNA的分布是相同的，并且几乎所有的GFP产生细胞都共表达MC4-R mRNA。例如，在下丘脑室旁核(PVH)和迷走神经背核(DMV)可见GFP和MC4-R的共同表达细胞。在分泌促甲状腺激素释放激素的PVH细胞和胆碱能DMV细胞中发现MC4-R启动子驱动的GFP表达。最后，我们观察到合成的MC3/4-R激动剂MT-II使一些表达GFP的细胞去极化，这表明MC4-Rs在某些情况下发挥突触后功能，在另一些情况下可能发挥突触前功能。这些研究扩大了我们对MC4-R的分布和功能的认识。转基因小鼠品系应该有助于进一步研究黑素皮质素信号在调节摄食行为和自主神经动态平衡中的作用。
The melanocortin-4 receptor (MC4-R) is an important regulator of energy homeostasis, and evidence suggests that MC4-R-expressing neurons are downstream targets of leptin action. MC4-Rs are broadly expressed in the CNS, and the distribution of MC4-R mRNA has been analyzed most extensively in the rat. However, relatively little is known concerning chemical profiles of MC4-R-expressing neurons. The extent to which central melanocortins act presynaptically or postsynaptically on MC4-Rs is also unknown. To address these issues, we have generated a transgenic mouse line expressing green fluorescent protein (GFP) under the control of the MC4-R promoter, using a modified bacterial artificial chromosome. We have confirmed that the CNS distribution of GFP-producing cells is identical to that of MC4-R mRNA in wild-type mice and that nearly all GFP-producing cells coexpress MC4-R mRNA. For example, cells coexpressing GFP and MC4-R mRNA were distributed in the paraventricular hypothalamic nucleus (PVH) and the dorsal motor nucleus of the vagus (DMV). MC4-R promotor-driven GFP expression was found in PVH cells producing thyrotropin-releasing hormone and in cholinergic DMV cells. Finally, we have observed that a synthetic MC3/4-R agonist, MT-II, depolarizes some GFP-expressing cells, suggesting that MC4-Rs function postsynaptically in some instances and may function presynaptically in others. These studies extend our knowledge of the distribution and function of the MC4-R. The transgenic mouse line should be useful for future studies on the role of melanocortin signaling in regulating feeding behavior and autonomic homeostasis.