Homozygous mice are viable but infertile. Fertility can be restored with enzyme replacement therapy. Less than 1% residual enzyme activity is observed. Homozygous mice are indistinguishable from wild type mice at birth, but show distinct growth retardation, shortened extremities, and facial dysmorphism observable at three months with a moderate increase in severity with age. Long bones of the lower extremities are shortened, broad, and sclerotic. Compared to wild-type, this model has increased urinary glycosaminoglycan and secondary elevation of other lysosomal storage enzymes. Further, homozygous mice show abundant lysosomal storage in liver, kidney, leptomeningeal cells, cornea, and retinal pigment epithelium. The phenotype exhibited by this mutant mouse strain is less severe than that observed in a similarly constructed mutant (Stock No. 005643) which bears a E536A point mutation. This strain represents a model of human GUS deficiency characterized by the most prevalent human mutation, L176F, and is associated with mild Mucopolysaccharidosis type VII (MPS VII or Sly Syndrome).
