A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease
Identifieur interne : 000467 ( Ncbi/Curation ); précédent : 000466; suivant : 000468A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease
Auteurs : Heike Wolf [Allemagne] ; Markus Damme [Allemagne] ; Stijn Stroobants [Belgique] ; Rudi D'Hooge [Belgique] ; Hans Christian Beck [Danemark] ; Irm Hermans-Borgmeyer [Allemagne] ; Renate Lüllmann-Rauch [Allemagne] ; Thomas Dierks [Allemagne] ; Torben Lübke [Allemagne]Source :
- Disease Models & Mechanisms [ 1754-8403 ] ; 2016.
Abstract
Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (
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DOI: 10.1242/dmm.025122
PubMed: 27491075
PubMed Central: 5047687
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D-24098</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stroobants, Stijn" sort="Stroobants, Stijn" uniqKey="Stroobants S" first="Stijn" last="Stroobants">Stijn Stroobants</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Laboratory of Biological Psychology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven B-3000</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="D Hooge, Rudi" sort="D Hooge, Rudi" uniqKey="D Hooge R" first="Rudi" last="D'Hooge">Rudi D'Hooge</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Laboratory of Biological Psychology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven 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Center Hamburg-Eppendorf</institution>,<addr-line>Hamburg D-20246</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lullmann Rauch, Renate" sort="Lullmann Rauch, Renate" uniqKey="Lullmann Rauch R" first="Renate" last="Lüllmann-Rauch">Renate Lüllmann-Rauch</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Department of Anatomy</addr-line>,<institution>University of Kiel</institution>,<addr-line>Kiel D-24098</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dierks, Thomas" sort="Dierks, Thomas" uniqKey="Dierks T" first="Thomas" last="Dierks">Thomas Dierks</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Biochemistry I, Department of Chemistry</addr-line>,<institution>Bielefeld University</institution>,<addr-line>Bielefeld D-33615</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lubke, Torben" sort="Lubke, Torben" uniqKey="Lubke T" first="Torben" last="Lübke">Torben Lübke</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Biochemistry I, Department of Chemistry</addr-line>,<institution>Bielefeld University</institution>,<addr-line>Bielefeld D-33615</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27491075</idno><idno type="pmc">5047687</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047687</idno><idno type="RBID">PMC:5047687</idno><idno type="doi">10.1242/dmm.025122</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000358</idno><idno type="wicri:Area/Pmc/Curation">000358</idno><idno type="wicri:Area/Pmc/Checkpoint">000073</idno><idno type="wicri:Area/Ncbi/Merge">000467</idno><idno type="wicri:Area/Ncbi/Curation">000467</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease</title><author><name sortKey="Wolf, Heike" sort="Wolf, Heike" uniqKey="Wolf H" first="Heike" last="Wolf">Heike Wolf</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Biochemistry I, Department of Chemistry</addr-line>,<institution>Bielefeld University</institution>,<addr-line>Bielefeld D-33615</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Damme, Markus" sort="Damme, Markus" uniqKey="Damme M" first="Markus" last="Damme">Markus Damme</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Biochemical Institute, University of Kiel</institution>,<addr-line>Kiel D-24098</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stroobants, Stijn" sort="Stroobants, Stijn" uniqKey="Stroobants S" first="Stijn" last="Stroobants">Stijn Stroobants</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Laboratory of Biological Psychology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven B-3000</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="D Hooge, Rudi" sort="D Hooge, Rudi" uniqKey="D Hooge R" first="Rudi" last="D'Hooge">Rudi D'Hooge</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Laboratory of Biological Psychology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven B-3000</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Beck, Hans Christian" sort="Beck, Hans Christian" uniqKey="Beck H" first="Hans Christian" last="Beck">Hans Christian Beck</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Biochemistry and Pharmacology</addr-line>,<institution>Centre for Clinical Proteomics, Odense University Hospital</institution>,<addr-line>Odense DK-5000</addr-line>,<country>Denmark</country></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hermans Borgmeyer, Irm" sort="Hermans Borgmeyer, Irm" uniqKey="Hermans Borgmeyer I" first="Irm" last="Hermans-Borgmeyer">Irm Hermans-Borgmeyer</name><affiliation wicri:level="1"><nlm:aff id="af5"><institution>ZMNH, University Medical Center Hamburg-Eppendorf</institution>,<addr-line>Hamburg D-20246</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lullmann Rauch, Renate" sort="Lullmann Rauch, Renate" uniqKey="Lullmann Rauch R" first="Renate" last="Lüllmann-Rauch">Renate Lüllmann-Rauch</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Department of Anatomy</addr-line>,<institution>University of Kiel</institution>,<addr-line>Kiel D-24098</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dierks, Thomas" sort="Dierks, Thomas" uniqKey="Dierks T" first="Thomas" last="Dierks">Thomas Dierks</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Biochemistry I, Department of Chemistry</addr-line>,<institution>Bielefeld University</institution>,<addr-line>Bielefeld D-33615</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lubke, Torben" sort="Lubke, Torben" uniqKey="Lubke T" first="Torben" last="Lübke">Torben Lübke</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Biochemistry I, Department of Chemistry</addr-line>,<institution>Bielefeld University</institution>,<addr-line>Bielefeld D-33615</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Disease Models & Mechanisms</title><idno type="ISSN">1754-8403</idno><idno type="eISSN">1754-8411</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (<italic>Fuca1</italic>) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abraham, D" uniqKey="Abraham D">D. Abraham</name></author><author><name sortKey="Blakemore, W F" uniqKey="Blakemore W">W. F. Blakemore</name></author><author><name sortKey="Dell, A" uniqKey="Dell A">A. Dell</name></author><author><name sortKey="Herrtage, M E" uniqKey="Herrtage M">M. E. 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Matsuda</name></author><author><name sortKey="Arashima, S" uniqKey="Arashima S">S. Arashima</name></author><author><name sortKey="Kobata, A" uniqKey="Kobata A">A. Kobata</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease
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