Connexin ␣ 1 , also referred to as Cx43, has thus far been the only gap junction protein identified between the hormone-producing cells of pancreatic islets. To investigate whether loss of this connexin affects the development of endocrine pancreas and the differentiation of insulin-producing  cells, we have taken advantage of a transgenic line in which the gene coding for connexin ␣ 1 had been functionally deleted by homologous recombination. Analysis of pancreas at embryonal day 19.5 (E19.5) after immunostaining for the four main types of islet hormones, showed that islet cell development was similar in homozygous transgenic mice that completely lacked ␣ 1 connexin, in mice that were heterozygous for the transgene, and in agematched controls with a genetic background similar to that of the transgenic animals. In particular, the three animal groups featured  cells that had a similar insulin content and ultrastructural organization, including the presence of typical gap junction plaques on the membrane. However, quantitative analysis of freeze-fractured membranes showed that these plaques were less frequent in the transgenic mice lacking ␣ 1 connexin. This finding prompted us to revisit the connexin pattern of normal pancreatic  cells. Using RT-PCR amplification and primers specific for nine of the mammalian connexins, we have found that normal rat and mouse pancreas contain six connexin transcripts, including one that codes for ␣ 6 connexin, a protein also referred to as Cx45. This transcript was also identified in isolated pancreatic islets, in FACS-purified suspensions of primary  cells and in the insulin-producing cells of an experimental tumor. Using antibodies, we found that connexin ␣ 6 is expressed by the latter cells, as well as by pancreatic fibroblasts and epithelial duct cells. The data show that pancreatic islets have a normal prenatal development in mice that no longer express ␣ 1 connexin. They further provide evidence that normal and tumoral insulinproducing cells natively coexpress connexins ␣ 1 and ␣ 6 .