Molecular basis of feline β-glucuronidase deficiency: An animal model of mucopolysaccharidosis VII

John C. Fyfe, Rebeccah L. Kurzhals, Mary Utter, Paula S. Henthorn, Prasad R.K. Alur, Ping Wang, John H. Wolfe, Urs Giger, Mark E. Haskins, Donald F. Patterson, Huaichang Sun, Sanjeev Jain, Naoya Yuhki

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


A family of domestic cats was found that exhibited clinical and biochemical abnormalities consistent with mucopolysaccharidosis VII, an autosomal recessive lysosomal storage disorder caused by β-glucuronidase deficiency. β-Glucuronidase activity was undetectable in affected cat fibroblasts and restored by retroviral gene transfer of rat β-glucuronidase cDNA. β-Glucuronidase mRNA was normal in affected cat testis by Northern blot analysis. Normal feline β-glucuronidase cDNA was cloned and characterized, and amplified from affected cat fibroblasts by reverse transcription coupled polymerase chain reaction. There was a G-to-A transition in the affected cat cDNA that predicted an E351K substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression studies. Multiple species comparison and the crystal structure of human β- glucuronidase indicated that E351 is a highly conserved residue most likely essential in maintenance of the enzyme's conformation. BssSI digestion of polymerase chain reaction products amplified from genomic DNA indicated that affected cats were homozygous and cats with half-normal β-glucuronidase activity were heterozygous for the missense mutation. Carriers identified in this manner produced affected kittens in prospective breedings, and a feline MPS VII breeding colony has been established.

Original languageEnglish (US)
Pages (from-to)121-128
Number of pages8
Issue number2
StatePublished - Jun 1 1999
Externally publishedYes


  • Animal model
  • Lysosomal storage disease
  • Missense mutation
  • Mucopolysaccharidosis
  • Mucopolysaccharidosis VII
  • β-glucuronidase

ASJC Scopus subject areas

  • Genetics


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