Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-aα deficiency

Roberta Resaz, Cristina Vanni, Daniela Segalerba, Angela R. Sementa, Luca Mastracci, Federica Grillo, Daniele Murgia, Maria Carla Bosco, Janice Y. Chou, Ottavia Barbieri, Luigi Varesio, Alessandra Eva

Research output: Contribution to journalArticlepeer-review


Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in glucose-6-phosphatase-aα (G6Pase-aα), and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs). A globally G6Pase-aα- deficient (G6pc-/-) mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liverspecific G6Pase-aα-deficient (LS-G6pc-/-) mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LSG6pc-/-mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS-G6pc-/-mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10-20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC). In conclusion, LS-G6pc-/-mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.

Original languageEnglish
Pages (from-to)1083-1091
Number of pages9
JournalDMM Disease Models and Mechanisms
Issue number9
Publication statusPublished - Sep 1 2014


  • Animal model
  • Glucose-6-phosphatase-aα
  • Glycogen storage disease type 1a
  • Hepatic steatosis
  • Hepatocellular adenoma
  • Hepatocellular carcinoma
  • Hepatomegaly

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Neuroscience (miscellaneous)
  • Medicine(all)


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