PMID- 10079507
OWN - NLM
STAT- MEDLINE
DCOM- 19990329
LR  - 20111117
IS  - 0192-253X (Print)
IS  - 0192-253X (Linking)
VI  - 24
IP  - 1-2
DP  - 1999
TI  - Loss of alpha 1 connexin does not alter the prenatal differentiation of
      pancreatic beta cells and leads to the identification of another islet cell
      connexin.
PG  - 13-26
AB  - 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.
FAU - Charollais, A
AU  - Charollais A
AD  - Department of Morphology, University of Geneva, Medical School, Centre Medical
      Universitaire, Switzerland.
FAU - Serre, V
AU  - Serre V
FAU - Mock, C
AU  - Mock C
FAU - Cogne, F
AU  - Cogne F
FAU - Bosco, D
AU  - Bosco D
FAU - Meda, P
AU  - Meda P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Genet
JT  - Developmental genetics
JID - 7909963
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (Insulin)
RN  - 0 (RNA, Messenger)
RN  - 0 (connexin 45)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Connexin 43/*genetics/physiology
MH  - Connexins/*genetics/physiology
MH  - Female
MH  - Gap Junctions/ultrastructure
MH  - Gene Expression
MH  - Insulin/analysis
MH  - Insulinoma/chemistry/genetics
MH  - Islets of Langerhans/chemistry/*cytology/embryology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Mutation
MH  - Pancreas/embryology
MH  - RNA, Messenger/analysis/genetics
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transgenes
MH  - Tumor Cells, Cultured
EDAT- 1999/03/18 03:02
MHDA- 2000/06/20 09:00
CRDT- 1999/03/18 03:02
PHST- 1999/03/18 03:02 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/03/18 03:02 [entrez]
AID - 10.1002/(SICI)1520-6408(1999)24:1/2<13::AID-DVG3>3.0.CO;2-N [pii]
AID - 10.1002/(SICI)1520-6408(1999)24:1/2<13::AID-DVG3>3.0.CO;2-N [doi]
PST - ppublish
SO  - Dev Genet. 1999;24(1-2):13-26. doi:
      10.1002/(SICI)1520-6408(1999)24:1/2<13::AID-DVG3>3.0.CO;2-N.