PMID- 10960441 OWN - NLM STAT- MEDLINE DCOM- 20000914 LR - 20231213 IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 32 IP - 3 DP - 2000 Sep TI - Hepatocarcinogenesis in female mice with mosaic expression of connexin32. PG - 501-6 AB - Mice deficient for connexin32 (Cx32), the major gap junction forming protein in liver, are highly susceptible to hepatocarcinogenesis. Because the Cx32 gene is located on the X-chromosome, heterozygous females show mosaicism with respect to Cx32 expression; this enables their use in studying the effect of Cx32-deficiency in a mixed Cx32-plus/Cx32-minus environment in vivo. Female C3H/He mice (Cx32(+/+)) were crossed with Cx32-deficient C57BL/129Sv males (Cx32(Y/-)) to yield F1 females heterozygous with respect to Cx32 (Cx32(+/-)). Patches of hepatocytes were observed in normal liver that either expressed Cx32 or failed to express the protein. The mean fraction of Cx32-negative tissue in liver was about 60% and did not change significantly with age of mice. Neoplastic liver lesions, induced in weanling mice, were identified in serial liver sections by their deficiency in glucose-6-phosphatase staining. Parallel sections were used for immunohistochemical demonstration of Cx32 protein. Smaller lesions were either homogenously Cx32-negative or showed unchanged to slightly elevated levels of Cx32 protein. There were no major differences in number and size distribution between lesions of these 2 phenotypes. In addition, larger lesions were mostly Cx32-negative but often contained embedded patches of Cx32-positive cells. Staining for the proliferation-associated nuclear antigen Ki-67 did not reveal significant differences between Cx32-negative and Cx32-positive hepatocytes in Cx32-mosaic tumors. This suggests that expression of Cx32 within a subpopulation of tumor cells does not negatively regulate their growth nor does it seem to affect the proliferation of their directly neighboring Cx32-negative counterparts. FAU - Moennikes, O AU - Moennikes O AD - Institut fur Toxikologie, Tubingen, Bonn, Germany. FAU - Buchmann, A AU - Buchmann A FAU - Willecke, K AU - Willecke K FAU - Traub, O AU - Traub O FAU - Schwarz, M AU - Schwarz M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (Connexins) SB - IM EIN - Hepatology 2000 Nov;32(5):1183 MH - Animals MH - Connexins/deficiency/*genetics MH - Female MH - Liver/metabolism/pathology MH - Liver Neoplasms/*genetics/pathology MH - Mice MH - Mice, Inbred C57BL MH - *Mosaicism MH - Gap Junction beta-1 Protein EDAT- 2000/08/29 11:00 MHDA- 2000/09/19 11:01 CRDT- 2000/08/29 11:00 PHST- 2000/08/29 11:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/08/29 11:00 [entrez] AID - S0270913900790100 [pii] AID - 10.1053/jhep.2000.16598 [doi] PST - ppublish SO - Hepatology. 2000 Sep;32(3):501-6. doi: 10.1053/jhep.2000.16598.