CLONING AND SEQUENCE-ANALYSIS OF THE MURINE GLUCAGON RECEPTOR-ENCODING GENE

CLONING AND SEQUENCE-ANALYSIS OF THE MURINE GLUCAGON RECEPTOR-ENCODING GENE
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DOI：
10.1016/0378-1119(95)00472-i
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发表时间：
1995-10-27
期刊：
GENE
影响因子：
3.5
通讯作者：
CHARRON, MJ
CHARRON, MJ
中科院分区：
生物学3区
文献类型：
--
作者：
BURCELIN, R;LI, J;CHARRON, MJ

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胰高血糖素受体（GR）通过控制肝脏葡萄糖生成和胰岛素分泌的速率，在调节血糖水平中起核心作用。为了通过分子遗传操作研究GR等候选基因在全身葡萄糖稳态中的综合作用，需要克隆该基因。我们克隆并测序了小鼠GR cDNA、基因和启动子区域，并研究了其组织分布。小鼠GR包含13个外显子，分布在4.0 kb的区域内。GR编码一种485个氨基酸的蛋白质，由7个假定的跨膜结构域组成。通过RT-PCR分析，我们发现GR主要在肝脏、肾脏、肾上腺、肺和胃中表达，而在棕色和白色脂肪组织、小脑、十二指肠和心脏中表达水平较低。此外，已对GR启动子的1000 bp区域进行了测序，其中包含与组织特异性（c/EBP； HNFI）或激素调节（类固醇受体）有关的推定dna结合蛋白的一致序列。其他已知在控制基础启动子活性中起作用的共识序列，如AP1、AP2和Sp1，也存在。相反，没有明显的塔塔或CAAT盒存在。我们在这里提供了重要的新信息，这对于未来在小鼠中进行基因操作是必要的。
The glucagon receptor (GR) plays a central role in regulating the level of blood glucose by controlling the rate of hepatic glucose production and insulin secretion. To study the integrated role of a candidate gene such as GR in whole-body glucose homeostasis by molecular genetic manipulation, cloning of the gene is required. We have cloned and sequenced the murine GR cDNA, gene and promoter region, and studied its tissue distribution. Murine GR contains 13 exons which are located in a region of 4.0 kb. GR encodes a 485-amino-acid protein that consists of seven putative transmembrane domains. By RT-PCR analysis, we have determined that GR is expressed predominantly in liver, kidney, adrenal, lung and stomach, while lower levels of expression are detected in brown and white adipose tissue, cerebellum, duodenum and heart. In addition, a 1000-bp region of the GR promoter has been sequenced which contains consensus sequences for putative DNA-binding proteins involved in tissue specificity (c/EBP; HNFI) or hormonal regulation (steroid receptor). Other consensus sequences known to function in controlling basal promoter activity, such as AP1, AP2 and Sp1, are also present. Conversely, no evident TATA or CAAT boxes are present. We provide here important new information necessary for the future pursuit of genetic manipulations in the mouse.