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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 646257, 9 pages
http://dx.doi.org/10.1155/2011/646257
Review Article

Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

1Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL 32610, USA
2Glycogen Storage Disease Program, Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA
3Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA
4Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL 32610, USA
5Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
6Animal Care Services, University of Florida, Gainesville, FL 32610, USA
7Section on Cellular Differentiation, PDEGEN, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD 20892, USA
8Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA
9Department of Pediatrics, University of Florida College of Medicine, P.O. Box 103610, Gainesville, FL 32610, USA

Received 6 October 2010; Accepted 24 November 2010

Academic Editor: Monica Fedele

Copyright © 2011 Andrew Specht et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.