Mouse Genome Informatics
hm1
    Gaatm1Rabn/Gaatm1Rabn
involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Abnormal lysosomal glycogen storage in heart and skeletal muscle of Gaatm1Rabn/Gaatm1Rabn mice

behavior/neurological
• severely impaired on a rotarod at 8-11 months of age
• in the wire-hang task, homozygous mutants perform poorly, indicating poor muscular function and grip strength
• at 15-16 weeks of age, homozygous mutant mice are almost never able to hold on to the inverted screen for more than 2 minutes
• starting at 3.5 weeks of age, display a striking reduction in vertical activity in the open field
• as early as 3.5 weeks of age, display reduced activity in the horizontal open field test, and consistently perform significantly worse than age-matched heterozygotes when placed in an open field environment (J:48839)
• develop abnormal field behavior within the first months of life (J:76435)
• at 7-9 months of age, display a weak, waddling gait (J:48839)
• by 16-18 months of age, display near paralysis of the hindlimbs and an abnormal footprint pathway

muscle
• accumulation of lysosomal glycogen in skeletal muscle (J:48839)
• in contrast to frozen quadricep muscles from wild-type mice which contain very little glycogen and >50% of their glycogen phosphorylase is in the form of phosphorylase-a (Ph-a), quadricep muscles from homozygous mutant mice have little or no Ph-a activity and contain 20 times or more glycogen (J:73924)
• massive accumulation of glycogen in skeletal muscle and diaphragm (J:76435)
• display a significant reduction in the number of myofibrils and lack of lateral myofibrillar registration
• signs of sarcomere degradation
• deformation of Z lines
• seen in older mice (8-9 months)
• at 7-9 months of age, homozygotes show obvious signs of muscle weakness and muscle wasting (J:48839)
• by 16-18 months, homozygotes exhibit a severe lower back muscle wasting and anterior muscle wasting (J:48839)
• develop a progressive muscle wasting disorder with clinical features of glycogen storage disease II; average age of onset is 7.1 months for females and 8.1 months for males

cardiovascular system

cellular
• at >3 weeks of age, cardiac and skeletal muscle lysosomes increase in size and number, and display increased density of accumulated glycogen particles
• at >3 weeks of age, some cardiac and skeletal muscle lysosomes appear broken, suggesting that leakage of lysosomal proteases may contribute to the damage of muscle structure

homeostasis/metabolism
• accumulation of lysosomal glycogen in the heart (J:48839)
• massive accumulation of glycogen in heart and brain (J:76435)
• accumulation of lysosomal glycogen in skeletal muscle (J:48839)
• in contrast to frozen quadricep muscles from wild-type mice which contain very little glycogen and >50% of their glycogen phosphorylase is in the form of phosphorylase-a (Ph-a), quadricep muscles from homozygous mutant mice have little or no Ph-a activity and contain 20 times or more glycogen (J:73924)
• massive accumulation of glycogen in skeletal muscle and diaphragm (J:76435)

skeleton
• by 16-18 months, homozygous mutant mice exhibit a striking kyphosis

Mouse Models of Human Disease
OMIM IDRef(s)
Glycogen Storage Disease II 232300 J:48839 , J:76435