cellular phenotype

• multifocal hepatic necrosis
  • many terminally ill homozygotes suffer from massive coagulative hepatic necrosis caused by bacterial infections
  (MGI Ref ID J:91114)

• abnormal lysosome morphology
  • at >18 months, homozygotes show widely distributed lysosomal hypertrophy both in the CNS and in visceral organs
  (MGI Ref ID J:91114)
  • as early as 5-10 months, homozygotes exhibit a massive accumulation of aspartylglucosamine along with lysosomal vacuolization
  (MGI Ref ID J:37022)
  • a strong accumulation of hypertrophic lysosomes is noted in the deep cerebellar nuclei whereas only relatively minor changes are observed in the hippocampus
  (MGI Ref ID J:49386)

homeostasis/metabolism phenotype

• abnormal urine homeostasis
  • AGU pathophysiologic features were reversed in non-neuronal tissues over a 2-week period of enzyme therapy
  (MGI Ref ID J:60272)
  • complete glycosylasparaginase deficiency leads to accumulation of aspartylglucosamine in tissues and urine
  (MGI Ref ID J:37022)
  • glycosylasparaginase activity increased to 10% of that in wild-type brain tissue and the accumulation of aspartylglucosamine was decreased by 20% in total brain of treated mice
  (MGI Ref ID J:60272)
  • a single AGA injection reduced the amount of aspartylglucosamine in liver and spleen by 90% and 80%, respectively
  (MGI Ref ID J:60272)
  • adult homozygotes receiving i.v. injections of recombinant glycosylasparaginase rapidly restore aspartylglucosamine to normal levels in non-neuronal tissues
  (MGI Ref ID J:60272)

• colorless urine
  • urine inside dilatated bladders is clear, not due to bacterial infections
  (MGI Ref ID J:91114)

• aspartylglucosaminuria
  • complete glycosylasparaginase deficiency leads to accumulation of aspartylglucosamine in urine
  (MGI Ref ID J:37022)

integument phenotype

• disheveled coat
  • at ~5 months, homozygotes start to exhibit a general scruffiness, recognizable from their disheveled coat
  (MGI Ref ID J:91114)

liver/biliary system phenotype

• multifocal hepatic necrosis
  • many terminally ill homozygotes suffer from massive coagulative hepatic necrosis caused by bacterial infections
  (MGI Ref ID J:91114)

mortality/aging

• premature death
  • the average lifespan of homozygous mutant mice is 19 months
  (MGI Ref ID J:91114)
  • the first spontaneous deaths occur at 10 months
  (MGI Ref ID J:91114)

nervous system phenotype

• abnormal axon morphology
  • at 5-10 months, homozygotes exhibit axonal swelling in the gracile nucleus
  (MGI Ref ID J:37022)

• astrocytosis
  • older mice (>18 months) show intensive astrogliosis
  (MGI Ref ID J:91114)

• abnormal cerebellum morphology
  • homozygotes display cerebellar damage, manifested as severe loss of Purkinje cells, intensive astrogliosis, and vacuolation of neurons in deep cerebellar nuclei
  (MGI Ref ID J:91114)

• neurodegeneration
  • severe vacuolation of cells in the vestibular and cochlear nuclei may contribute to the impairment of neuromotor coordination
  (MGI Ref ID J:91114)
  • in older homozygotes (>18 months), severe neuronal vacuolation is often associated with neuronal loss
  (MGI Ref ID J:91114)
  • neuronal vacuolation is pronounced in the lateral thalamic nuclei, medullary reticular nuclei, vestibular nuclei, inferior olivary complex, and deep cerebellar nuclei
  (MGI Ref ID J:91114)

• neurogenic bladder
  • at >18 months, all aging homozygotes suffer from impaired bladder function
  (MGI Ref ID J:91114)
  • as peripheral nerves remain unaffected, the "neurogenic bladder" phenotype is presumed to be secondary to the CNS defects
  (MGI Ref ID J:91114)

• Purkinje cell degeneration
  • unlike AGU patients, where loss of Purkinje cells is scattered, homozygotes display widespread loss of Purkinje cells
  (MGI Ref ID J:91114)

renal/urinary system phenotype

• abnormal urine homeostasis
  • AGU pathophysiologic features were reversed in non-neuronal tissues over a 2-week period of enzyme therapy
  (MGI Ref ID J:60272)
  • complete glycosylasparaginase deficiency leads to accumulation of aspartylglucosamine in tissues and urine
  (MGI Ref ID J:37022)
  • a single AGA injection reduced the amount of aspartylglucosamine in liver and spleen by 90% and 80%, respectively
  (MGI Ref ID J:60272)
  • adult homozygotes receiving i.v. injections of recombinant glycosylasparaginase rapidly restore aspartylglucosamine to normal levels in non-neuronal tissues
  (MGI Ref ID J:60272)
  • glycosylasparaginase activity increased to 10% of that in wild-type brain tissue and the accumulation of aspartylglucosamine was decreased by 20% in total brain of treated mice
  (MGI Ref ID J:60272)

• abnormal renal glomerulus morphology
  • homozygotes display glomerular loss
  (MGI Ref ID J:91114)

• hydronephrosis
  • impaired bladder function and subsequent hydronephrosis are often associated with a reflux nephropathy
  (MGI Ref ID J:91114)

• distended urinary bladder
  • a significant number of older male homozygotes have massively swollen bladders
  (MGI Ref ID J:37022)

• kidney atrophy
  • renal parenchyma is thinned
  (MGI Ref ID J:91114)

• renal interstitial fibrosis
  • homozygotes exhibit interstitial fibrosis
  (MGI Ref ID J:91114)

• aspartylglucosaminuria
  • complete glycosylasparaginase deficiency leads to accumulation of aspartylglucosamine in urine
  (MGI Ref ID J:37022)

• abnormal kidney calyx morphology
  • the caliceal mucosa is distended to one or two urothelial cells
  (MGI Ref ID J:91114)

• abnormal urinary bladder urothelium morphology
  • the thickness of the urothelium varies with the degree of bladder distention, stretching to a thickness of two cells in the most distended area
  (MGI Ref ID J:91114)

• colorless urine
  • urine inside dilatated bladders is clear, not due to bacterial infections
  (MGI Ref ID J:91114)

• renal tubule atrophy
  • homozygotes display tubular atrophy
  (MGI Ref ID J:91114)

• neurogenic bladder
  • at >18 months, all aging homozygotes suffer from impaired bladder function
  (MGI Ref ID J:91114)
  • as peripheral nerves remain unaffected, the "neurogenic bladder" phenotype is presumed to be secondary to the CNS defects
  (MGI Ref ID J:91114)

• anuria
  • homozygotes fail to urinate, leading to a massive expansion of the bladder
  (MGI Ref ID J:91114)

behavior/neurological phenotype

• impaired limb coordination
  • at 18 months or older, homozygotes often drag their hind legs while walking
  (MGI Ref ID J:91114)

• ataxia
  • older homozygotes (>18 months) show a severe ataxic gait
  (MGI Ref ID J:91114)

• impaired coordination
  • at 18 months or older, homozygotes show impaired neuromotor coordination
  (MGI Ref ID J:91114)
  • at the age of 5 to 10 months, homozygotes exhibit impaired neuromotor coordination
  (MGI Ref ID J:37022)

• impaired balance
  • at 18 months or older, homozygotes exhibit great difficulty moving as well as poor balance
  (MGI Ref ID J:91114)

• short stride length
  • older homozygotes (>18 months) display short steps and often walk straddle-legged
  (MGI Ref ID J:91114)