alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase cDNA and identification of a missense mutation causing alpha-mannosidosis

Biochim Biophys Acta. 2002 Mar 16;1586(2):169-76. doi: 10.1016/s0925-4439(01)00081-3.


alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of the lysosomal alpha-mannosidase. We report here the sequencing and expression of the lysosomal alpha-mannosidase cDNA from normal and alpha-mannosidosis guinea pigs. The amino acid sequence of the guinea pig enzyme displayed 82-85% identity to the lysosomal alpha-mannosidase in other mammals. The cDNA of the alpha-mannosidosis guinea pig contained a missense mutation, 679C>T, leading to substitution of arginine by tryptophan at amino acid position 227 (R227W). The R227W allele segregated with the alpha-mannosidosis genotype in the guinea pig colony and introduction of R227W into the wild-type sequence eliminated the production of recombinant alpha-mannosidase activity in heterologous expression studies. Furthermore, the guinea pig mutation has been found in human patients. Our results strongly indicate that the 679C>T mutation causes alpha-mannosidosis and suggest that the guinea pig will be an excellent model for investigation of pathogenesis and evaluation of therapeutic strategies for human alpha-mannosidosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • COS Cells / metabolism
  • Cloning, Molecular
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / chemistry
  • Disease Models, Animal
  • Genetic Therapy
  • Guinea Pigs
  • Mannosidases / biosynthesis
  • Mannosidases / chemistry
  • Mannosidases / genetics*
  • Molecular Sequence Data
  • Mutation, Missense*
  • Sequence Alignment
  • Species Specificity
  • alpha-Mannosidase
  • alpha-Mannosidosis / enzymology
  • alpha-Mannosidosis / genetics*


  • DNA, Complementary
  • Mannosidases
  • alpha-Mannosidase