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

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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.