{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:54:35Z","timestamp":1790805275641,"version":"4.1.0"},"reference-count":45,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3425,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12, and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.<\/jats:p>","DOI":"10.1242\/dmm.009712","type":"journal-article","created":{"date-parts":[[2012,6,27]],"date-time":"2012-06-27T15:34:48Z","timestamp":1340811288000},"source":"Crossref","is-referenced-by-count":27,"title":["Characterization of a canine model of glycogen storage disease type IIIa"],"prefix":"10.1242","author":[{"given":"Haiqing","family":"Yi","sequence":"first","affiliation":[{"name":"Duke University, Durham, NC, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth L.","family":"Thurberg","sequence":"additional","affiliation":[{"name":"Genzyme Corporation, Framingham, MA, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Curtis","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Austin","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Fyfe","sequence":"additional","affiliation":[{"name":"Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight D.","family":"Koeberl","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya S.","family":"Kishnani","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baodong","family":"Sun","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2021042500582958900_b1-0050804","first-page":"282","article-title":"Serum creatine phosphokinase as an indicator of muscle injury after various spinal and nonspinal surgical procedures","volume":"7","author":"Arts","year":"2007","journal-title":"J. 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Hepatol."},{"key":"2021042500582958900_b7-0050804","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1210\/endo-42-6-454","article-title":"Histological observations on the relation of insulin to the deposition of glycogen in adipose tissue","volume":"42","author":"Fawcett","year":"1948","journal-title":"Endocrinology"},{"key":"2021042500582958900_b8-0050804","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s10545-007-0485-2","article-title":"Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX","volume":"30","author":"Geberhiwot","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"2021042500582958900_b9-0050804","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S1542-3565(05)00416-7","article-title":"Increased liver chemistry in an asymptomatic patient","volume":"3","author":"Goessling","year":"2005","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"2021042500582958900_b10-0050804","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1939-1676.2007.tb02926.x","article-title":"Glycogen storage disease type IIIa in curly-coated retrievers","volume":"21","author":"Gregory","year":"2007","journal-title":"J. Vet. Intern. Med."},{"key":"2021042500582958900_b11-0050804","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/hep.510250307","article-title":"Type IIIb glycogen storage disease associated with end-stage cirrhosis and hepatocellular carcinoma","volume":"25","author":"Haagsma","year":"1997","journal-title":"Hepatology"},{"key":"2021042500582958900_b12-0050804","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1023\/A:1005687323096","article-title":"Blood lipids and endothelial function in glycogen storage disease type III","volume":"22","author":"Hershkovitz","year":"1999","journal-title":"J. Inherit. Metab. Dis."},{"key":"2021042500582958900_b13-0050804","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/GIM.0b013e3181cd735b","article-title":"The electrodiagnostic characteristics of Glycogen Storage Disease Type III","volume":"12","author":"Hobson-Webb","year":"2010","journal-title":"Genet Med."},{"key":"2021042500582958900_b14-0050804","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0021-9258(18)38503-X","article-title":"Structure of glycogens and amylopectins. III. Normal and abnormal human glycogen","volume":"199","author":"Illingworth","year":"1952","journal-title":"J. Biol. Chem."},{"key":"2021042500582958900_b15-0050804","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0021-9258(18)65877-6","article-title":"Amylo-1,6-glucosidase in muscle tissue in generalized glycogen storage disease","volume":"218","author":"Illingworth","year":"1956","journal-title":"J. Biol. Chem."},{"key":"2021042500582958900_b16-0050804","doi-asserted-by":"crossref","first-page":"E952","DOI":"10.1152\/ajpendo.00559.2006","article-title":"Transgenic overexpression of protein targeting to glycogen markedly increases adipocytic glycogen storage in mice","volume":"292","author":"Jurczak","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2021042500582958900_b17-0050804","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1097\/MPG.0b013e31820e6a55","article-title":"Markedly elevated serum transaminases in glycogen storage disease type III","volume":"52","author":"Karwowski","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"2021042500582958900_b18-0050804","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1172\/JCI1722","article-title":"Clinical and metabolic correction of pompe disease by enzyme therapy in acid maltase-deficient quail","volume":"101","author":"Kikuchi","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2021042500582958900_b19-0050804","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3350\/kjhep.2008.14.2.219","article-title":"An adult case of glycogen storage disease type IIIa","volume":"14","author":"Kim","year":"2008","journal-title":"Korean J. Hepatol."},{"key":"2021042500582958900_b20-0050804","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1354\/vp.38-1-83","article-title":"Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia)","volume":"38","author":"Kishnani","year":"2001","journal-title":"Vet. Pathol."},{"key":"2021042500582958900_b21-0050804","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1097\/GIM.0b013e3181e655b6","article-title":"Glycogen storage disease type III diagnosis and management guidelines","volume":"12","author":"Kishnani","year":"2010","journal-title":"Genet. 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Cardiol."},{"key":"2021042500582958900_b25-0050804","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1097\/00005176-199703000-00008","article-title":"Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature","volume":"24","author":"Labrune","year":"1997","journal-title":"J. Pediatric Gastroenterol. Nutr."},{"key":"2021042500582958900_b26-0050804","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/BF02436768","article-title":"Plasma creatine kinase and cardiomyopathy in glycogen storage disease type III","volume":"18","author":"Lee","year":"1995","journal-title":"J. Inherit. Metab. Dis."},{"key":"2021042500582958900_b27-0050804","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S0002-9149(96)00885-5","article-title":"Comparison of the functional significance of left ventricular hypertrophy in hypertrophic cardiomyopathy and glycogenosis type III","volume":"79","author":"Lee","year":"1997","journal-title":"Am. J. Cardiol."},{"key":"2021042500582958900_b28-0050804","first-page":"72","article-title":"Clinical, biochemical and genetic features of glycogen debranching enzyme deficiency","volume":"26","author":"Lucchiari","year":"2007","journal-title":"Acta Myol."},{"key":"2021042500582958900_b29-0050804","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1177\/002215540505300108","article-title":"High-resolution light microscopy (HRLM) and digital analysis of Pompe disease pathology","volume":"53","author":"Lynch","year":"2005","journal-title":"J Histochem. Cytochem."},{"key":"2021042500582958900_b30-0050804","first-page":"E796","article-title":"Liver glycogen turnover in fed and fasted humans","volume":"266","author":"Magnusson","year":"1994","journal-title":"Am. J. Physiol."},{"key":"2021042500582958900_b31-0050804","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mce.2009.08.013","article-title":"Stranger in a strange land: roles of glycogen turnover in adipose tissue metabolism","volume":"318","author":"Markan","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021042500582958900_b32-0050804","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1136\/hrt.34.8.862","article-title":"Gross cardiac involvement in glycogen storage disease type 3","volume":"34","author":"Miller","year":"1972","journal-title":"Br. Heart J."},{"key":"2021042500582958900_b33-0050804","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/ajmg.1320420514","article-title":"Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis","volume":"42","author":"Momoi","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"2021042500582958900_b34-0050804","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1007\/BF00443106","article-title":"Cardiac involvement in glycogen storage disease type III","volume":"148","author":"Moses","year":"1989","journal-title":"Eur. J. Pediatr."},{"key":"2021042500582958900_b35-0050804","doi-asserted-by":"crossref","first-page":"28824","DOI":"10.1074\/jbc.M102192200","article-title":"Identification of the catalytic residues of bifunctional glycogen debranching enzyme","volume":"276","author":"Nakayama","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021042500582958900_b36-0050804","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/ajcp\/50.1.29","article-title":"Glycogen metabolism and storage diseases of types III, IV and V","volume":"50","author":"Pearson","year":"1968","journal-title":"Am. J. Clin. Pathol."},{"key":"2021042500582958900_b37-0050804","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00004836-200004000-00011","article-title":"Respective value of alkaline phosphatase, gamma-glutamyl transpeptidase and 5\u2032 nucleotidase serum activity in the diagnosis of cholestasis: a prospective study of 80 patients","volume":"30","author":"Sapey","year":"2000","journal-title":"J. Clin. Gastroenterol."},{"key":"2021042500582958900_b38-0050804","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1002\/ajmg.a.32529","article-title":"Clinicopathological analysis of the homozygous p.W1327X AGL mutation in glycogen storage disease type 3","volume":"146A","author":"Schoser","year":"2008","journal-title":"Am. J. Med. Genet."},{"key":"2021042500582958900_b39-0050804","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/00004836-200007000-00020","article-title":"Hepatocellular carcinoma complicating liver cirrhosis in type IIIa glycogen storage disease","volume":"31","author":"Siciliano","year":"2000","journal-title":"J. Clin. Gastroenterol."},{"key":"2021042500582958900_b40-0050804","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1432-1033.1975.tb03911.x","article-title":"Debranching enzyme from rabbit skeletal muscle","volume":"51","author":"Taylor","year":"1975","journal-title":"Eur. J. Biochem."},{"key":"2021042500582958900_b41-0050804","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1113\/jphysiol.1942.sp003950","article-title":"Glycogen and adipose tissue","volume":"100","author":"Tuerkischer","year":"1942","journal-title":"J. Physiol."},{"key":"2021042500582958900_b42-0050804","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1432-1033.1967.tb00134.x","article-title":"The subgroups of type 3 glycogenosis","volume":"2","author":"Van Hoof","year":"1967","journal-title":"Eur. J. Biochem."},{"key":"2021042500582958900_b43-0050804","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj2810021","article-title":"Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the \u2018phosphocreatine circuit\u2019 for cellular energy homeostasis","volume":"281","author":"Wallimann","year":"1992","journal-title":"Biochem. 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