E2A GENE-PRODUCTS ARE NOT REQUIRED FOR INSULIN GENE-EXPRESSION

Transcripts for E2A gene products, ubiquitous basic helix-loop-helix t ransactivating proteins, are expressed at high levels in the pancreati c epithelium. E2A proteins have been shown to bind the cognate E box s equence (CANNTG) of the insulin promoter/enhancer. E2A gene products d imerize with cell-specific basic helix-loop-helix proteins and synergi ze with the homeodomain transcription factor, PDX-1, in insulin gene t ransactivation. PDX-1 is also required For normal pancreatic developme nt in mice, We investigated whether pancreatic development acid insuli n production could occur in the absence of E2A, gene products by study ing mice with a null mutation for the gene. E2A(-/-) mice demonstrated normal formation of pancreatic endocrine and exocrine tissue in histo chemical 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 significa nt difference in blood glucose levels or pancreatic insulin content co mpared with wild-type littermates. These data show that although E2A g ene products probably play an important role in insulin gene expressio n, pancreatic development and insulin production can proceed in their absence.