title: Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.
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.
authors.affiliation: Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Specht
authors.forename: Laurie
authors.initials: L
authors.lastname: Fiske
authors.forename: Kirsten
authors.initials: K
authors.lastname: Erger
authors.forename: Travis
authors.initials: T
authors.lastname: Cossette
authors.forename: John
authors.initials: J
authors.lastname: Verstegen
authors.forename: Martha
authors.initials: M
authors.lastname: Campbell-Thompson
authors.forename: Maggie B
authors.initials: MB
authors.lastname: Struck
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Lee
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Chou
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Correia
authors.forename: Cathryn S
authors.initials: CS
authors.lastname: Mah
authors.forename: David A
authors.initials: DA
authors.lastname: Weinstein
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Conlon
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics* / Q000378:metabolism*; D004285:Dogs; D005953:Glycogen Storage Disease Type I / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary; D006801:Humans; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism* / Q000662:veterinary