Human Molecular Genetics, Vol 8, 1365-1372, Copyright © 1999 by Oxford University Press
S Stinchi, R Lullmann-Rauch, D Hartmann, R Coenen, T Beccari, A Orlacchio, K von Figura and P Saftig
Alpha-mannosidosis is a lysosomal storage disease with autosomal recessive
inheritance caused by a deficiency of the lysosomal alpha- mannosidase,
which is involved in the degradation of asparagine-linked carbohydrate
cores of glycoproteins. An alpha-mannosidosis mouse model was generated by
targeted disruption of the gene for lysosomal alpha- mannosidase.
Homozygous mutant animals exhibit alpha-mannosidase enzyme deficiency and
elevated urinary secretion of mannose-containing oligosaccharides.
Thin-layer chromatography revealed an accumulation of oligosaccharides in
liver, kidney, spleen, testis and brain. The cellular alterations were
characterized by multiple membrane-limited cytoplasmic vacuoles as seen for
instance in liver, exocrine pancreas, kidney, thyroid gland, smooth muscle
cells, osteocytes and in various neurons of the central and peripheral
nervous systems. The morphological lesions and their topographical
distribution, as well as the biochemical alterations, closely resemble
those reported for human alpha-mannosidosis. This mouse model will be a
valuable tool for studying the pathogenesis of inherited alpha-mannosidosis
and may help to evaluate therapeutic approaches for lysosomal storage
diseases.
ARTICLES
Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis
Dipartimento di Biologia Cellulare e Molecolare, Sezione di Biochimica e Biologia Molecolare, Universita degli Studi di Perugia, Via del Giochetto, 06126 Perugia, Italy,
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