Itkin-Ansari P, Bain G, Beattie G M, Murre C, Hayek A, Levine F
Center for Molecular Genetics, Whittier Institute, Department of Pediatrics, University of California-San Diego School of Medicine 92093-0634, USA.
Endocrinology. 1996 Aug;137(8):3540-3. doi: 10.1210/endo.137.8.8754784.
Transcripts for E2A gene products, ubiquitous basic helix-loop-helix transactivating proteins, are expressed at high levels in the pancreatic epithelium. E2A proteins have been shown to bind the cognate E box sequence (CANNTG) of the insulin promoter/enhancer. E2A gene products dimerize with cell-specific basic helix-loop-helix proteins and synergize with the homeodomain transcription factor, PDX-1, in insulin gene transactivation. PDX-1 is also required for normal pancreatic development in mice. We investigated whether pancreatic development and insulin production could occur in the absence of E2A gene products by studying mice with a null mutation for the gene. E2A(-/-) mice demonstrated normal formation of pancreatic endocrine and exocrine tissue in histochemical sections as well as positive and distinct immunostaining for insulin and glucagon in islet tissue, signifying development of mature beta- and alpha-cells. Moreover, E2A(-/-) mice displayed no significant difference in blood glucose levels or pancreatic insulin content compared with wild-type littermates. These data show that although E2A gene products probably play an important role in insulin gene expression, pancreatic development and insulin production can proceed in their absence.
E2A基因产物是普遍存在的碱性螺旋-环-螺旋转录激活蛋白，其转录本在胰腺上皮中高水平表达。E2A蛋白已被证明可结合胰岛素启动子/增强子的同源E盒序列（CANNTG）。E2A基因产物与细胞特异性碱性螺旋-环-螺旋蛋白二聚化，并在胰岛素基因转录激活中与同源结构域转录因子PDX-1协同作用。PDX-1对小鼠正常胰腺发育也是必需的。我们通过研究该基因发生无效突变的小鼠，来探究在没有E2A基因产物的情况下胰腺发育和胰岛素产生是否会发生。E2A（-/-）小鼠在组织化学切片中显示胰腺内分泌和外分泌组织正常形成，胰岛组织中胰岛素和胰高血糖素的免疫染色呈阳性且明显，表明成熟β细胞和α细胞发育。此外，与野生型同窝小鼠相比，E2A（-/-）小鼠的血糖水平或胰腺胰岛素含量没有显著差异。这些数据表明，尽管E2A基因产物可能在胰岛素基因表达中起重要作用，但在没有它们的情况下胰腺发育和胰岛素产生仍可进行。
