Pathological features of glycogen storage disease type II highlighted in the knockout mouse model

Glycogen storage disease type II (GSDII; Pompe's disease) is an autosomal r ecessive disease caused by lysosomal alpha-glucosidase deficiency. Skeletal muscle weakness is the most conspicuous clinical symptom of patients suffe ring from GSDII and skeletal muscle also is prominently involved in the kno ckout mouse model of this disease. Thus far, however, little detailed infor mation has been published on the pathological changes in other mouse tissue s. This paper aims to provide these data and gives a record of the clinical course of the mouse model over a 2-year period. Four-month-old affected mi ce perform worse in a running wheel than their unaffected littermates, but do not yet display other clear signs of disease. The lysosomal glycogen sto rage, already evident at birth, becomes more severe in time, leading to mus cle wasting by 9-10 months of age and then limb girdle weakness and kyphosi s. The disease does not markedly shorten the animal's life span despite the serious tissue pathology, which is not limited to heart and skeletal muscl e, but is also seen in the smooth muscle of blood vessels and of the respir atory, digestive, and urogenital tracts. In addition, the mice have lysosom al glycogen storage in the liver, kidney, spleen, and salivary gland; in Sc hwann cells of the peripheral nerves, and in a subset of neurons in the cen tral nervous system. By pathological criteria, the knockout mouse model par allels the human infantile form of GSDII and is attractive for studying the possible reversal of tissue pathology and symptomatology under different t herapeutic regimes. Copyright (C) 1999 John Wiley & Sons, Ltd.