STRUCTURE AND FUNCTION OF NOVEL GENE (BRG1) EXPRESSED IN PANCREATIC BETA CELLS

胰腺β细胞表达的新基因（BRG1）的结构和功能

基本信息

批准号：
11671131
负责人：
HAMAGUCHI Kazuyuki
金额：
$ 1.92万
依托单位：
OITA MEDICAL UNIVERISTY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671131/
关键词：
pancreatic β cell differential display type 1 diabetes MIN6 TNF-α 1型糖尿病 HLA スピードコンジェニック NODマウス cDNA

项目摘要

Utilizing the differential display technique with arbitrarily-primed PCR, we obtained a 〜500bp fragment, which is preferentially amplified in the cDNA from mouse β cell lines. We named the gene as BRG1 (β related gene 1). The mRNA was very large, I.e. 〜14kb, and the levels of expression were higher in the groups cultured with high glucose than low glucose in MIN6 cells and rat islets. Tissue distribution of BRG1 mRNA expression revealed that BRG1 gene was expressed ubiquitously in various mouse tissues. The highest expression was observed in the testes. The almost entire region of 〜14kb cDNA was sequenced and determined. There were 87〜89 % sequence identities between the mouse and the human sequences. On the other hand, sequence identities between mouse and Drosophila BRG1 sequence were 67〜74 % in each of 5 restricted regions of about 84〜324 bp stretches. The deduced BRG1 amino acid sequences for mouse and human (〜4, 400 A.A.) had 93.8 % identity throughout the entire region. On the other hand, there was 41.8 % identity in the C-terminal 〜3,800 amino acid region between mouse and Drosophila BRG1 protein. Moreover, there was 26.8 % identity in the C-terminal 〜1,650 amino acid region between mouse and C. elegans BRG1 protein. The chromosomal mapping of the BRG1 gene using the mouse RH panel revealed that the BRG1 is located at the distal part of mouse chromosome 4, where one of the diabetogenic genes in NOD mouse, Iddll, has been mapped.The second research theme was about the polymorphisms in the 5'-flanking region of the tumor necrosis factor (TNF)-α gene in Japanese type 1 diabetes. We observed that the TNFP-D and -B alleles were associated with type 1 diabetes, which may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles.

利用与任意提出的PCR的差分显示技术，我们获得了约500bp的片段，在小鼠β细胞系中更优选地在cDNA中放大了片段。我们将该基因命名为BRG1（β相关的基因1）。 mRNA非常大，即〜14Kb，在高葡萄糖培养的基团中，在MIN6细胞和大鼠胰岛中培养的基团的表达水平高。 BRG1 mRNA表达的组织分布表明，BRG1基因在各种小鼠组织中无处不在。在测试中观察到最高的表达。测序并确定了〜14Kb cDNA的几乎整个区域。小鼠和人类序列之间存在87-89％的序列身份。另一方面，在约84-324 bp的5个限制区域中，小鼠和果蝇BRG1序列之间的序列身份均为67-74％。小鼠和人类的推导BRG1氨基酸序列（〜4,400 A.A.）在整个地区具有93.8％的身份。另一方面，在小鼠和果蝇BRG1蛋白之间的C末端〜3,800氨基酸区域中有41.8％的身份。此外，在小鼠和秀丽隐杆线虫BRG1蛋白之间的C端〜1,650氨基酸区域中有26.8％的身份。使用小鼠RH面板对BRG1基因的染色体映射表明，BRG1位于小鼠染色体染色体的盘式部分，其中一个是NOD小鼠IDDLL中的糖尿病基因基因，已被映射。第二个研究主题是关于5'-flank the Tumor necriss ine tumor necrosis的5'-flank fimormorpormiss in tumor necrosis的多态性（TNE）。我们观察到TNFP -D和-B等位基因与1型糖尿病有关，这可能是其与易感HLA I类和II类等位基因的连锁二驱动有关的继发的。