Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (13)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Sun, M.-S.
Right arrow Articles by Chou, J. Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, M.-S.
Right arrow Articles by Chou, J. Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 18 2155-2164
© 2002 Oxford University Press

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

Mao-Sen Sun1, Chi-Jiunn Pan1, Jeng-Jer Shieh1, Abhijit Ghosh1, Li-Yuan Chen1, Brian C. Mansfield1, Jerrold M. Ward2, Barry J. Byrne3 and Janice Yang Chou1,*

1Section on Cellular Differentiation, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA, 2Veterinary and Tumor Pathology Section, Office of Laboratory Animal Science, National Cancer Institute, Frederick, MD 21702, USA and 3Powell Gene Therapy Center and Department of Pediatrics and Molecular Genetics & Microbiology, University of Florida, Gainesville, FL 32610, USA

Received May 3, 2002; Revised June 28, 2002; Accepted June 28, 2002

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.

* To whom correspondence should be addressed at: Building 10, Room 9S241, NIH, 9000 Rockville Pike, Bethesda, MD 20892-1830, USA. Tel: +1 3014961094; Fax: +1 3014026035; Email: chou{at}helix.nih.gov


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
L.-Y. Chen, J.-J. Shieh, B. Lin, C.-J. Pan, J.-L. Gao, P. M. Murphy, T. F. Roe, S. Moses, J. M. Ward, E. J. Lee, et al.
Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter
Hum. Mol. Genet., October 1, 2003; 12(19): 2547 - 2558.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.