At birth, mice that are homozygous for the targeted allele are viable, normal in size and do not display any gross physical or behavioral abnormalities. Low levels of transcript are detectable, but functional protein is absent. By 3 weeks of age, light microscopy (PAS staining) reveals a progressive accumulation of lysosomal glycogen in heart and skeletal muscle, and diaphragm. Concomitant with accumulating glycogen is a significant reduction in the number of myofibrils and signs of damaged muscle structure. Reduced mobility and progressive muscle weakness is observed by 3-4 weeks of age. By 8-9 months of age, muscle glycogen storage and progressive muscle weakness are obvious but do not become clinically evident until 12 months of age, delaying clinical assessment of treatment efficacy. Adults are fertile. These mice recapitulate key features of glycogen storage disease type II (GSDII) and provide a model for studying the underlying mechanism of GSDII.
Of note, C57BL/6NJ-Gaatm1Jhng/J mice, available as Stock No. 034609, also survive into adulthood, however they carry a mutation orthologous to one found in human IOPD making it much “closer” in genetic homology to human Pompe Disease.
