English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Conditional knockout mice, based on the Cre-loxP system, are a widely used model for examining organ-specific gene functions. To date, efficient hepatocyte-specific knockout has been reported in many different models, but little attention has been paid to the long-term stability of the recombination efficiency. In the present study, we characterized Alb-Cre;Ctnnb1flox/flox 'hepatocyte-specific Ctnnb1 knockout' mice of different ages to test whether efficient recombination is maintained over time. At 2 months of age, the knockout mouse livers achieved efficient deletions of β-catenin in hepatocytes. However, as the mice aged, the reappearance and expansion of β-catenin-expressing hepatocytes were observed. In 1-year-old mice, a significant proportion of the pericentral hepatocytes in the knockout mouse livers were replaced with β-catenin-positive hepatocytes, whereas the periportal hepatocytes mostly remained β-catenin-negative. Furthermore, most of the 1-year-old mice spontaneously developed hepatocellular adenomas and carcinomas that were positive for β-catenin and overexpressed glutamine synthetase and Slc1a2, both of which are hallmarks of active β-catenin signaling. Sequencing analysis revealed that the Ctnnb1 alleles were not inactivated but had activating mutations in these tumors. The present study suggests that recombination efficiency should be carefully examined when hepatocyte-specific knockout mice of different ages are analyzed. In addition, illegitimate deletion mutations should be recognized as potential adverse effects of the Cre-loxP system.

Hepatomas with activating Ctnnb1 mutations in ‘ Ctnnb1 -deficient’ livers: a tricky aspect of a conditional knockout mouse model