Hepatocarcinogenesis in female mice with mosaic expression of connexin32

Hepatology. 2000 Sep;32(3):501-6. doi: 10.1053/jhep.2000.16598.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Connexins / deficiency
  • Connexins / genetics*
  • Female
  • Gap Junction beta-1 Protein
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mosaicism*

Substances

  • Connexins