PMID- 16740338
OWN - NLM
STAT- MEDLINE
DCOM- 20060926
LR  - 20231213
IS  - 0171-9335 (Print)
IS  - 0171-9335 (Linking)
VI  - 85
IP  - 8
DP  - 2006 Aug
TI  - Ablation of gap junctional communication in hepatocytes of transgenic mice does 
      not lead to disrupted cellular homeostasis or increased spontaneous 
      tumourigenesis.
PG  - 717-28
AB  - Gap junctions between murine hepatocytes are composed of two subunit proteins, 
      connexin26 (Cx26) and connexin32 (Cx32). Previously, we found increased formation 
      of chemically induced liver tumours but no increase in spontaneous development of 
      preneoplastic hepatic foci in mice that lacked Cx32 and expressed decreased 
      amounts of Cx26. In order to clarify this tumour-suppressive effect and to 
      overcome embryonic lethality of constitutive Cx26-deficient mice, cell 
      type-specific targeting of the Cx26 gene was performed. Mice with loxP-flanked 
      Cx26 coding DNA were crossed with mice expressing the Cre recombinase exclusively 
      in hepatocytes. Progeny mice lacking Cx26 in the liver were viable and fertile 
      with no obvious signs of phenotypic alterations. To generate mice that totally 
      lack gap junctional intercellular coupling, these mice were crossed with 
      constitutive Cx32-deficient mice. We found no increase in spontaneously induced 
      liver tumour formation in Cx26 and double deficient Cx26/Cx32 mice. Occasionally, 
      double deficient livers exhibited morphological alterations, like amyloidosis, 
      and a slightly increased basal proliferation rate of hepatocytes. Although the 
      absence of gap junction channels led to altered expression of adhesion-related 
      proteins like E-cadherin and actin, microarray analyses of total liver 
      transcripts yielded only few differences between Cx26-deficient and double 
      deficient livers compared to control samples. Our results suggest that total lack 
      of gap junctional communication due to hepatocytic ablation of Cx26 and Cx32 does 
      not drastically alter basal hepatocytic function and does not lead to increased 
      spontaneous liver tumour formation.
FAU - Ott, Thomas
AU  - Ott T
AD  - Institut fur Genetik, Abteilung Molekulargenetik, Universitat Bonn, Romerstr. 
      164, D-53117 Bonn, Germany.
FAU - Jokwitz, Melanie
AU  - Jokwitz M
FAU - Lenhard, Diana
AU  - Lenhard D
FAU - Romualdi, Alessandro
AU  - Romualdi A
FAU - Dombrowski, Frank
AU  - Dombrowski F
FAU - Ittrich, Carina
AU  - Ittrich C
FAU - Schwarz, Michael
AU  - Schwarz M
FAU - Willecke, Klaus
AU  - Willecke K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060605
PL  - Germany
TA  - Eur J Cell Biol
JT  - European journal of cell biology
JID - 7906240
RN  - 0 (Carcinogens)
RN  - 0 (Connexins)
RN  - 127120-53-0 (Connexin 26)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Carcinogens/toxicity
MH  - Cell Communication/physiology
MH  - Cell Proliferation/drug effects
MH  - Connexin 26
MH  - Connexins/deficiency/genetics/*physiology
MH  - Diethylnitrosamine/pharmacology
MH  - Female
MH  - Gap Junctions/genetics/*physiology
MH  - Hepatocytes/cytology/drug effects/*metabolism
MH  - Homeostasis/genetics/*physiology
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Liver/cytology/drug effects/metabolism
MH  - Liver Neoplasms, Experimental/chemically induced/genetics/pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Gap Junction beta-1 Protein
EDAT- 2006/06/03 09:00
MHDA- 2006/09/27 09:00
CRDT- 2006/06/03 09:00
PHST- 2006/01/05 00:00 [received]
PHST- 2006/03/23 00:00 [revised]
PHST- 2006/03/27 00:00 [accepted]
PHST- 2006/06/03 09:00 [pubmed]
PHST- 2006/09/27 09:00 [medline]
PHST- 2006/06/03 09:00 [entrez]
AID - S0171-9335(06)00066-5 [pii]
AID - 10.1016/j.ejcb.2006.03.004 [doi]
PST - ppublish
SO  - Eur J Cell Biol. 2006 Aug;85(8):717-28. doi: 10.1016/j.ejcb.2006.03.004. Epub 
      2006 Jun 5.