Mouse Genome Informatics
involves: 129S4/SvJae * C57BL/6
phenotype observed in females
phenotype observed in males
N normal phenotype
• homozygous mutants were viable and fertile, and displayed normal behavior and movement up to 11 months of age
• both young and aged homozygotes displayed normal motor performance during swimming
• aged homozygotes did not perform quite as well as control mice in the Morris water maze hidden platform test, indicating a defect in spatial learning and memory
• homozygotes exhibited slow worsening of performance with age

• at 6 weeks, mutants displayed accumulation of hypertrophic storage lysosomes in the brain, liver, kidney and skin
• extensive accumulation of storage lysosomes was already evident pre-natally
• vacuolized lysosomes were evident in the livers of homozygous fetuses at 19 days, whereas only few, small vacuoles were detectable in fetuses of 14 days; in contrast, cells in brain sections of 19 day fetuses showed only scanty small vacuoles, whereas in 6-week-old mice the vacuolization in brain cells was extensive
• the diameter of storage lysosomes varied from 0.2 to 4 Ám in most organs, and up to 8 Ám in the liver
• in brain, lysosomal storage vacuoles were detected in the neurons and glia of the neocortical and cortical regions

• at 4-7 months, mutant mice of both sexes had body weights 20% higher than age-matched control littermates

• as a result of complete enzyme deficiency, mutants excreted aspartylglucosamine in their urine

renal/urinary system
• as a result of complete enzyme deficiency, mutants excreted aspartylglucosamine in their urine

nervous system
• MRI images of living homozygotes revealed signal intensity changes, including enlarged cerebrospinal fluid spaces and hypointensity of the deep gray matter structures
• atrophy of the cerebral hemispheres resulted in enlarged ventricles
• atrophy of the cerebral hemispheres

Mouse Models of Human Disease
Aspartylglucosaminuria; AGU 208400 J:45587