Loss of XXXX does not alter the prenatal differentiation of pancreatic beta cells and leads to the identification of another islet cell connexin.

@entity1 @entity16899 @entity19 @entity5 @entity10062 @entity35 @entity17704
Connexin alpha 1, also referred to as @entity16899 , 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 beta cells, we have taken advantage of a transgenic line in which the gene coding for connexin alpha 1 had been functionally deleted by homologous recombination. Analysis of pancreas at embryonal day 19.5 (E 19.5) after immunostaining for the four main types of islet hormones, showed that islet cell development was similar in homozygous @entity19 that completely lacked @entity16899 , in @entity19 that were heterozygous for the transgene, and in age-matched controls with a genetic background similar to that of the transgenic animals. In particular, the three animal groups featured beta 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 @entity19 lacking @entity16899 . This finding prompted us to revisit the connexin pattern of normal pancreatic beta cells. Using RT-PCR amplification and primers specific for nine of the @entity1 connexins, we have found that normal @entity35 and @entity19 pancreas contain six connexin transcripts, including one that codes for alpha 6 connexin, a protein also referred to as @entity17704 . This transcript was also identified in isolated pancreatic islets, in @entity10062 -purified suspensions of primary beta cells and in the insulin-producing cells of an experimental @entity5 . Using antibodies, we found that connexin alpha 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 @entity19 that no longer express @entity16899 . They further provide evidence that normal and tumoral insulin-producing cells natively coexpress connexins alpha 1 and alpha 6.
