{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:10Z","timestamp":1787018350722,"version":"build-2736575974"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK056014,DK056016"],"award-info":[{"award-number":["DK056014,DK056016"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina","award":["P30 CA138313,P30 GM103339"],"award-info":[{"award-number":["P30 CA138313,P30 GM103339"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,8]]},"abstract":"<jats:p>\n                    Gaucher disease, the most prevalent lysosomal storage disease, is caused by homozygous mutations at the\n                    <jats:italic>GBA<\/jats:italic>\n                    gene, which is responsible for encoding the enzyme glucocerebrosidase. Neuronopathic Gaucher disease is associated with microgliosis, astrogliosis, and neurodegeneration. However, the role that microglia, astrocytes, and neurons play in the disease remains to be determined. In the current study, we developed inducible, cell-type-specific\n                    <jats:italic>Gba<\/jats:italic>\n                    -KO mice to better understand the individual impacts of\n                    <jats:italic>Gba<\/jats:italic>\n                    deficiencies on microglia and neurons.\n                    <jats:italic>Gba<\/jats:italic>\n                    was conditionally knocked out either exclusively in microglia or neurons or throughout the body. These mouse models were developed using a tamoxifen-inducible Cre system, with tamoxifen administration commencing at weaning. Microglia-specific\n                    <jats:italic>Gba<\/jats:italic>\n                    -KO mice showed no signs of disease. However, the neuron-specific\n                    <jats:italic>Gba<\/jats:italic>\n                    KO resulted in a shortened lifespan, severe weight loss, and ataxia. These mice also had significant neurodegeneration, microgliosis, and astrogliosis accompanied by the accumulation of glucosylceramide and glucosylsphingosine, recapitulating Gaucher disease\u2013like symptoms. These surprising findings reveal that, unlike the neuron-specific\n                    <jats:italic>Gba<\/jats:italic>\n                    deficiency, microglia-specific\n                    <jats:italic>Gba<\/jats:italic>\n                    deficiency alone does not induce disease. The neuronal Gaucher disease mouse model, with a median survival of 16 weeks, may be useful for future studies of pathogenesis and the evaluation of therapies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.179126","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T16:02:21Z","timestamp":1727107341000},"source":"Crossref","is-referenced-by-count":8,"title":["Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model"],"prefix":"10.1172","volume":"9","author":[{"given":"Hannah B.D.","family":"Duffy","sequence":"first","affiliation":[{"name":"Genetics of Development and Disease Section, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA."},{"name":"Department of Pharmacology, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Byrnes","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Section, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Section, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Tuymetova","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Section, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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