Loss of α<sub>1</sub> connexin does not alter the prenatal differentiation of pancreatic β cells and leads to the identification of another islet cell connexin

Article Article scientifique Article Loss of α<sub>1</sub> connexin does not alter the prenatal differentiation of pancreatic β cells and leads to the identification of another islet cell connexin eng 1999 author Charollais Anne 23109 author Serre Beinier Véronique 0000-0002-6016-1645 123229 Département de chirurgie (CHIRU) author Mock Corina 41187 author Cogne-Gros Fabienne Catherine 29743 author Bosco Domenico 23285 author Meda Paolo 26346 13-26 10.1002/(SICI)1520-6408(1999)24:1/2<13::AID-DVG3>3.0.CO;2-N 10079507 0192-253X Connexin alpha 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 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 transgenic mice that completely lacked alpha 1 connexin, in mice 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 transgenic mice lacking alpha 1 connexin. 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 mammalian connexins, we have found that normal rat and mouse pancreas contain six connexin transcripts, including one that codes for alpha 6 connexin, a protein also referred to as Cx45. This transcript was also identified in isolated pancreatic islets, in FACS-purified suspensions of primary beta cells and in the insulin-producing cells of an experimental tumor. 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 mice that no longer express alpha 1 connexin. They further provide evidence that normal and tumoral insulin-producing cells natively coexpress connexins alpha 1 and alpha 6. Animals Cell Differentiation Connexin 43 / genetics Connexin 43 / physiology Connexins / genetics Connexins / physiology Female Gap Junctions / ultrastructure Gene Expression Insulin / analysis Insulinoma / chemistry Insulinoma / genetics Islets of Langerhans / chemistry Islets of Langerhans / cytology Islets of Langerhans / embryology Islets of Langerhans / metabolism Male Mice Mice, Inbred Strains Mice, Knockout Mice, Transgenic Mutation Pancreas / embryology RNA, Messenger / analysis RNA, Messenger / genetics Rats Reverse Transcriptase Polymerase Chain Reaction Transgenes Tumor Cells, Cultured Dewey 610 Dewey 616 Swiss National Science Foundation Connexin Expression and the Regulation of Islet Cell Development,Growth and Secretion. 53720 CH 4f7589ed-e44d-4850-a4d8-b0c1eccdfe48 Centre de recherche translationnelle en onco-hématologie 209 56 Département de médecine 221 false 902 Cancer du poumon et mésothéliome pleural malin 944 Developmental genetics 24 1-2 1d5aa176-2422-49c5-ba80-a32a7d1d9bf5 Article (Published version) Restricted Developmental_Genetics_-_1999_-_Cha.pdf 668801 application/pdf 9f348d8fb63d7982d572b1883b34616d05d742e2f2392a6d3535cdeb0fe68b3d restrictedAccess Faculté de médecine / Centre de recherche translationnelle en onco-hématologie Faculté de médecine / Section de médecine clinique / Département de médecine

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Loss of α₁ connexin does not alter the prenatal differentiation of pancreatic β cells and leads to the identification of another islet cell connexin	Developmental genetics			1999	4	0

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