Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-α activity restored are at risk of developing hepatic tumors.
- Goo-Young Kim,
- Young Mok Lee,
- Joon Hyun Kwon,
- Jun-Ho Cho,
- Chi-Jiunn Pan,
- Matthew F Starost,
- Brian C Mansfield,
- Janice Y Chou
Mol Genet Metab 2017 Jan 10. Epub 2017 Jan 10.
Section on Cellular Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States. Electronic address:
Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown. Read More