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.