The extent of synchronous initiation and termination of DNA synthesis in regenerating mouse liver is dependent on connexin32 expressing gap junctions.
OBJECTIVE
It has previously been shown in rat liver that the gap junctional proteins connexin32 and connexin26 are downregulated when murine hepatocytes are in the S-phase of the cell cycle. Therefore, it has been hypothesized that loss of functional gap junctions could affect proliferation of hepatocytes. This study aimed to check this hypothesis.


METHODS
We searched for differences in liver regeneration after two-thirds partial hepatectomy between connexin32-deficient and wild-type mice.


RESULTS
The ratio of liver to body weight in regenerating liver was not affected by loss of the connexin32 gene. The peak of DNA synthesis occurred at the same time, i.e. 36 to 96 h after partial hepatectomy, in connexin32-deficient and wild-type liver. During this time, however, only about half as many nuclei of hepatocytes in connexin32-deficient liver incorporated bromodeoxyuridine, compared to wild-type liver. Furthermore, 1-2 weeks after full recovery of liver mass, we detected a higher level of bromodeoxyuridine incorporation into hepatocytes of connexin32-deficient than in wild-type liver.


CONCLUSIONS
Loss of connexin32 protein and/or diminished expression of connexin26 did not promote G0/1-S transition of hepatocytes in two-thirds hepatectomized mouse livers. Instead, the extent of synchronous initiation and termination of DNA synthesis in regenerating liver was altered in connexin32-deficient mice.
Temme
A
A
Institut für Genetik, Abt. Molekulargenetik, University of Bonn, Germany.
Ott
T
T
Dombrowski
F
F
Willecke
K
K
D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000096:biosynthesis* / Q000235:genetics; D017629:Gap Junctions / Q000235:genetics; D005786:Gene Expression Regulation; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D000097002:Gap Junction beta-1 Protein
D000072259:Connexin 26; D017630:Connexins; D004247:DNA; D000097002:Gap Junction beta-1 Protein