Biochemical genetics of the Lapland dog model of glycogen storage disease type II (acid alpha-glucosidase deficiency).
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.
D000818:Animals; D002478:Cells, Cultured; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics; D004285:Dogs; D005816:Genetic Complementation Test; D005959:Glucosidases / Q000172:deficiency*; D006008:Glycogen Storage Disease / Q000662:veterinary*; D006801:Humans; D006822:Hybrid Cells / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D000520:alpha-Glucosidases / Q000172:deficiency* / Q000276:immunology
D005959:Glucosidases; D000520:alpha-Glucosidases