{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:05:47Z","timestamp":1792033547261,"version":"4.4.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-148863"],"award-info":[{"award-number":["PJT-148863"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009056","name":"Canadian Glycomics Network","doi-asserted-by":"crossref","award":["CD-2"],"award-info":[{"award-number":["CD-2"]}],"id":[{"id":"10.13039\/501100009056","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009056","name":"Canadian Glycomics Network","doi-asserted-by":"crossref","award":["ID-01"],"award-info":[{"award-number":["ID-01"]}],"id":[{"id":"10.13039\/501100009056","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,23]]},"abstract":"<jats:p>\n                    Sialidosis is an ultra-rare multisystemic lysosomal disease caused by mutations in the neuraminidase 1 (\n                    <jats:italic>NEU1<\/jats:italic>\n                    ) gene. The severe type II form of the disease manifests with a prenatal\/infantile or juvenile onset, bone abnormalities, severe neuropathology, and visceromegaly. A subset of these patients present with nephrosialidosis, characterized by abrupt onset of fulminant glomerular nephropathy. We studied the pathophysiological mechanism of the disease in 2 NEU1-deficient mouse models, a constitutive\n                    <jats:italic>Neu1<\/jats:italic>\n                    -knockout,\n                    <jats:italic>Neu1<\/jats:italic>\n                    <jats:italic\/>\n                    <jats:sup>\u0394Ex3<\/jats:sup>\n                    <jats:italic\/>\n                    , and a conditional phagocyte-specific knockout,\n                    <jats:italic>Neu1<\/jats:italic>\n                    <jats:sup>\n                      Cx3cr1\n                      <jats:italic>\u0394<\/jats:italic>\n                      Ex3\n                    <\/jats:sup>\n                    <jats:italic\/>\n                    . Mice of both strains exhibited terminal urinary retention and severe kidney damage with elevated urinary albumin levels, loss of nephrons, renal fibrosis, presence of storage vacuoles, and dysmorphic mitochondria in the intraglomerular and tubular cells. Glycoprotein sialylation in glomeruli, proximal distal tubules, and distal tubules was drastically increased, including that of an endocytic reabsorption receptor megalin. The pool of megalin bearing O-linked glycans with terminal galactose residues, essential for protein targeting and activity, was reduced to below detection levels. Megalin levels were severely reduced, and the protein was directed to lysosomes instead of the apical membrane. Together, our results demonstrated that desialylation by NEU1 plays a crucial role in processing and cellular trafficking of megalin and that NEU1 deficiency in sialidosis impairs megalin-mediated protein reabsorption.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.166470","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T12:01:07Z","timestamp":1694520067000},"source":"Crossref","is-referenced-by-count":22,"title":["Severe kidney dysfunction in sialidosis mice reveals an essential role for neuraminidase 1 in reabsorption"],"prefix":"10.1172","volume":"8","author":[{"given":"Ikhui","family":"Kho","sequence":"first","affiliation":[{"name":"CHU Sainte-Justine Research Center, University of Montreal, Montreal, Qu\u00e9bec, Canada."},{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal, Qu\u00e9bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina 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