Bovine glycogenosis type II: the molecular defect in Shorthorn cattle.

The molecular defect in Shorthorn cattle affected with glycogenosis type II was studied. Polyclonal and monoclonal antibodies specific for bovine skeletal muscle acid alpha-glucosidase were raised and used to study the molecular and biochemical defect in seven affected animals. Cultured normal bovine fibroblasts pulsed and chased with [3H] leucine produced a 130 kDa precursor form of acid alpha-glucosidase which was processed via several 100 kDa intermediate forms to the 65 kDa mature form within 26 h. Fibroblasts from affected animals were labelled in vitro and were shown to produce a cross-reactive protein which was identified as the precursor form of the enzyme. The mature form of the enzyme was not found. The precursor form of the enzyme was demonstrated in Western blots of muscle tissue extracts from affected animals. Glycogenosis type II in Shorthorn and Brahman cattle must be caused by a different, independent maturation, since Brahman cattle lack the cross-reactive protein for acid alpha-glucosidase.