Biochemical genetics of the Lapland dog model of glycogen storage disease type II (acid alpha-glucosidase deficiency)

• Published in: American journal of medical genetics Vol. 19; no. 3; p. 589
• Main Authors: Walvoort, H C, Slee, R G, Sluis, K J, Koster, J F, Reuser, A J
• Format: Journal Article
• Language: English
• Published: United States 01.11.1984
• Subjects: alpha-Glucosidases - deficiency; alpha-Glucosidases - immunology; Animals; Cells, Cultured; Dog Diseases - enzymology; Dog Diseases - genetics; Dogs; Genetic Complementation Test; Glucosidases - deficiency; Glycogen Storage Disease - veterinary; Humans; Hybrid Cells - enzymology; Liver - enzymology
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/ajmg.1320190323

A recently described canine model (Lapland dog) of glycogen storage disease type II (GSD II, Pompe disease, acid alpha-glucosidase deficiency) was identified with several biochemical genetic methods. Complementation studies in which fibroblasts from a GSD II dog were fused with fibroblasts derived from control dogs and from human patients with different clinical forms of the disease did not lead to restoration of acid alpha-glucosidase activity in the heterokaryon cell populations. These results indicate that acid alpha-glucosidase deficiency is the primary defect in canine GSD II and that there is a close genetic parallelism with human GSD II. Immunotitration analysis of the residual acid alpha-glucosidase activity in the canine GSD II fibroblasts and liver demonstrated that this residual activity was not due to acid alpha-glucosidase enzyme, in which respect canine GSD II was similar to the infantile form of the human disease. Double immunodiffusion studies showed the presence of catalytically inactive acid alpha-glucosidase enzyme protein in canine GSD II. This is consistent with a structural gene mutation. It is concluded that canine GSD II in the Lapland dog is a homologous model of the infantile form of human GSD II, a conclusion in concordance with clinical and pathological studies.