Journal Article

Sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen storage disease type Ia in mice

Mao-Sen Sun, Chi-Jiunn Pan, Jeng-Jer Shieh, Abhijit Ghosh, Li-Yuan Chen, Brian C. Mansfield, Jerrold M. Ward, Barry J. Byrne and Janice Yang Chou

in Human Molecular Genetics

Volume 11, issue 18, pages 2155-2164
Published in print September 2002 | ISSN: 0964-6906
Published online September 2002 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/11.18.2155
Sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen storage disease type Ia in mice

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Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type Ia (GSD-Ia), an autosomal recessive disorder characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. G6Pase is an endoplasmic reticulum-associated transmembrane protein expressed primarily in the liver and the kidney. Therefore, enzyme replacement therapy is not feasible using current strategies, but somatic gene therapy, targeting G6Pase to the liver and the kidney, is an attractive possibility. Previously, we reported the development of a mouse model of G6Pase deficiency that closely mimics human GSD-Ia. Using neonatal GSD-Ia mice, we now demonstrate that a combined adeno virus and adeno-associated virus vector-mediated gene transfer leads to sustained G6Pase expression in both the liver and the kidney and corrects the murine GSD-Ia disease for at least 12 months. Our results suggest that human GSD-Ia would be treatable by gene therapy.

Journal Article.  6771 words.  Illustrated.

Subjects: Genetics and Genomics

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