Mice homozygous for the Sgshmps3a mutation have only 3-4% of the wild type level of sulfamidase activity. This results in extensive lysosomal accumulation of heparin sulfate most prominently in neuronal tissue and liver and, to a lesser degree, in the spleen. GM2 ganglioside accumulation is also found. The outward phenotype of scruffy coat, hunched posture, and reduced activity is usually seen by 6 to 7 months of age. Corneal opacity is also found at approximately 7 months of age. Death occurs between 7 and 10 months of age, on average, and autopsy reveals brain lesions, hepatosplenomegaly and a distended bladder containing turbid urine. The homozygotes have thicker skullcaps, vertebral deformation, thickening of the urinary bladder wall, and bladder blockage that leads to severe bladder distention as they age. Sgshmps3a /Sgshmps3a mice provide a model for the human disease mucopolysaccharidosis 3A (MPSIIIA), also known as Sanfilippo syndrome type A. The electrophoresis banding pattern of glycosaminoglycans from the brain and urine of homozygous mice is similar to the abnormal pattern found in samples from human MPSIIIA patients. The human disease symptoms include severe central nervous system degeneration, claw hand, and visceromegaly, with death occurring in the second or third decade of life. Please see OMIM for more details. (Bhaumik et al., 1999; Bhattacharyya et al., 2001.)
