HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

Abstract
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.
AuthorsThomas Berg, John J Hopwood
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1586 Issue 2 Pg. 169-76 (Mar 16 2002) ISSN: 0006-3002 [Print] Netherlands
PMID11959458 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Complementary
  • Mannosidases
  • alpha-Mannosidase
Topics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • COS Cells (metabolism)
  • Cloning, Molecular
  • DNA, Complementary (biosynthesis, chemistry)
  • Disease Models, Animal
  • Genetic Therapy
  • Guinea Pigs
  • Mannosidases (biosynthesis, chemistry, genetics)
  • Molecular Sequence Data
  • Mutation, Missense
  • Sequence Alignment
  • Species Specificity
  • alpha-Mannosidase
  • alpha-Mannosidosis (enzymology, genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: