Abstract
The dominant negative effect of mutations is rare in metabolic diseases and its mechanism has not been studied much. Hypophosphatasia, a bone inherited metabolic disorder, is a good model because the disease can be dominantly transmitted. The gene product activity depends on a homodimeric configuration and many mutations have been reported in the ALPL gene responsible for the disease. Using CFP/YFP-tagged-TNSALP plasmids, transfections in COS cells and confocal fluorescence analyses, we studied the point mutation G232V (c.746G>T). We showed that the G232V protein sequestrates some of the wild-type protein into the cells and prevents it from reaching the membrane where it plays its physiological role.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / chemistry
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Alkaline Phosphatase / genetics*
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Alkaline Phosphatase / metabolism*
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Amino Acid Substitution
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Animals
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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COS Cells
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Chlorocebus aethiops
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Female
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Genes, Dominant*
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Green Fluorescent Proteins / chemistry
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Heterozygote
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Humans
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Hypophosphatasia / enzymology*
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Hypophosphatasia / genetics*
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Infant
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Infant, Newborn
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Luminescent Proteins / chemistry
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Male
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Microscopy, Fluorescence
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Models, Genetic
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Mutation, Missense*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Subcellular Fractions / enzymology
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Transfection
Substances
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Bacterial Proteins
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Cyan Fluorescent Protein
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Luminescent Proteins
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Recombinant Fusion Proteins
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yellow fluorescent protein, Bacteria
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Green Fluorescent Proteins
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Alkaline Phosphatase