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|Title:||α-Mannosidosis in the guinea pig: cloning of the lysosomal α-mannosidase cDNA and identification of a missense mutation causing α-mannosidosis|
|Other Titles:||Alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase cDNA and identification of a missense mutation causing alpha-mannosidosis|
|Citation:||Biochimica et Biophysica Acta-Molecular Basis of Disease, 2002; 1586(2):169-176|
|Publisher:||Elsevier Science BV|
|Thomas Berg and John J. Hopwood|
|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.|
|Keywords:||COS Cells; Animals; Guinea Pigs; alpha-Mannosidosis; Disease Models, Animal; Mannosidases; alpha-Mannosidase; DNA, Complementary; Cloning, Molecular; Sequence Alignment; Species Specificity; Binding Sites; Amino Acid Sequence; Base Sequence; Mutation, Missense; Molecular Sequence Data; Genetic Therapy|
|Description:||Copyright © 2001 Elsevier Science B.V. All rights reserved.|
|Appears in Collections:||Paediatrics publications|
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