{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:44:50Z","timestamp":1765442690274,"version":"3.46.0"},"reference-count":82,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanofi and NIH NIAMS","award":["R01AR065932"],"award-info":[{"award-number":["R01AR065932"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gaucher disease (GD), caused by biallelic pathogenic variants in GBA1, has evolved from being understood as a macrophage-restricted lysosomal disorder to a multisystem condition involving neuroinflammation, immune dysregulation, and cell-type-specific lipid toxicity. This expanded view has driven a parallel progression in GD mouse model development. Early chemically induced and germline knockout models provided foundational insights but were limited by perinatal lethality or incomplete phenotypic fidelity. Subsequent generations of conditional, inducible, and lineage-specific models enabled dissection of visceral and neuronopathic manifestations and clarified the contributions of macrophages, B cells, neurons, microglia, osteoblasts, and endothelial cells to disease pathogenesis. More recent humanized immune and gene-edited platforms, together with multi-omics integration, now allow modeling of genotype-specific biology and therapeutic response with greater translational precision. In this review, we synthesize the evolution of GD mouse models across these eras, evaluate their strengths and limitations, and highlight species-specific challenges including differences in lipid metabolism, immune architecture, and the absence of the GBAP1 pseudogene in mice that influence interpretation and clinical translation. We outline emerging strategies for incorporating patient-derived mutations, modifier pathways, and clinically meaningful endpoints into future models. Our aim is to provide a coherent framework that bridges murine and human GD biology and supports the development of more predictive platforms to accelerate mechanistic discovery, biomarker development, and therapeutic innovation across all subtypes of GD.<\/jats:p>","DOI":"10.3390\/ijms262411915","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T14:22:40Z","timestamp":1765376560000},"page":"11915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Refining Mouse Models of Gaucher Disease: Advancing Mechanistic Insights, Biomarker Discovery, and Therapeutic Strategies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-3129","authenticated-orcid":false,"given":"Nima","family":"Fattahi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiapeng","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Belinsky","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pramod K.","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiny","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","unstructured":"Valle, D.L., Antonarakis, S., Ballabio, A., Beaudet, A.L., and Mitchell, G.A. (2019). Gaucher Disease. The Online Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill Education."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19473","DOI":"10.1073\/pnas.1003308107","article-title":"Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage","volume":"107","author":"Mistry","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ginhoux, F., Lim, S., Hoeffel, G., Low, D., and Huber, T. (2013). Origin and differentiation of microglia. Front. Cell. Neurosci., 7.","DOI":"10.3389\/fncel.2013.00045"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e79830","DOI":"10.7554\/eLife.79830","article-title":"Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy","volume":"11","author":"Boddupalli","year":"2022","journal-title":"Elife"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/357407a0","article-title":"Animal model of Gaucher\u2019s disease from targeted disruption of the mouse glucocerebrosidase gene","volume":"357","author":"Tybulewicz","year":"1992","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13819","DOI":"10.1073\/pnas.0606016103","article-title":"Effective cell and gene therapy in a murine model of Gaucher disease","volume":"103","author":"Enquist","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17483","DOI":"10.1073\/pnas.0708086104","article-title":"Murine models of acute neuronopathic Gaucher disease","volume":"104","author":"Enquist","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pewzner-Jung, Y., Joseph, T., Blumenreich, S., Vardi, A., Ferreira, N.S., Cho, S.M., Eilam, R., Tsoory, M., Biton, I.E., and Brumfeld, V. (2021). Brain pathology and cerebellar purkinje cell loss in a mouse model of chronic neuronopathic Gaucher disease. Prog. Neurobiol., 197.","DOI":"10.1016\/j.pneurobio.2020.101939"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymgme.2020.12.291","article-title":"Gaucher disease: Basic and translational science needs for more complete therapy and management","volume":"132","author":"Grabowski","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Woo, E.G., Tayebi, N., and Sidransky, E. (2021). Next-Generation Sequencing Analysis of GBA1: The Challenge of Detecting Complex Recombinant Alleles. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.684067"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.1073\/pnas.86.13.5049","article-title":"Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences","volume":"86","author":"Tokoro","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1086\/367850","article-title":"Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: Implications for complexity in Gaucher disease","volume":"72","author":"Tayebi","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Guo, J.N., Guan, M., Jiang, N., Li, N., Li, Y.J., Zhang, J., and Ma, D. (2022). Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially Humanized Gba1 Gene and F213I Mutation. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.892457"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/S0140-6736(95)91680-6","article-title":"Genotype\/phenotype correlations in Gaucher\u2019s disease","volume":"346","author":"Mistry","year":"1995","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2200553119","DOI":"10.1073\/pnas.2200553119","article-title":"A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebrosidase activity within live cells","volume":"119","author":"Deen","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.aan6298","article-title":"Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes","volume":"358","author":"Wyant","year":"2017","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ydbio.2021.10.007","article-title":"The origin and evolution of gene targeting","volume":"481","author":"Capecchi","year":"2022","journal-title":"Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nm.3853","article-title":"Translational value of mouse models in oncology drug development","volume":"21","author":"Gould","year":"2015","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.expneurol.2010.07.023","article-title":"Intracerebroventricular delivery of glucocerebrosidase reduces substrates and increases lifespan in a mouse model of neuronopathic Gaucher disease","volume":"225","author":"Bercury","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/mt.2008.9","article-title":"Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis","volume":"16","author":"Chang","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/brain\/awac379","article-title":"Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: The LEAP trial","volume":"146","author":"Schiffmann","year":"2023","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/mt.2016.53","article-title":"CNS-accessible Inhibitor of Glucosylceramide Synthase for Substrate Reduction Therapy of Neuronopathic Gaucher Disease","volume":"24","author":"Marshall","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1002\/ajh.26276","article-title":"Clinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results","volume":"96","author":"Mistry","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15428","DOI":"10.1073\/pnas.192582899","article-title":"Chemical chaperones increase the cellular activity of N370S \u03b2-glucosidase: A therapeutic strategy for Gaucher disease","volume":"99","author":"Sawkar","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/j.1471-4159.1978.tb12395.x","article-title":"The Gaucher mouse: Differential action of conduritol B epoxide and reversibility of its effects","volume":"30","author":"Stephens","year":"1978","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/mthe.2002.0650","article-title":"Demonstration of feasibility of in vivo gene therapy for Gaucher disease using a chemically induced mouse model","volume":"6","author":"Marshall","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/path.4751","article-title":"Delineating pathological pathways in a chemically induced mouse model of Gaucher disease","volume":"239","author":"Vardi","year":"2016","journal-title":"J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/j.celrep.2016.07.085","article-title":"Identification of Modifier Genes in a Mouse Model of Gaucher Disease","volume":"16","author":"Klein","year":"2016","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0950-3536(97)80036-4","article-title":"Gaucher\u2019s disease: The best laid schemes of mice and men","volume":"10","author":"Sidransky","year":"1997","journal-title":"Baillieres Clin. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1172\/JCI117160","article-title":"Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease","volume":"93","author":"Holleran","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1242\/dmm.008185","article-title":"Animal models for Gaucher disease research","volume":"4","author":"Vitner","year":"2011","journal-title":"Dis. Models Mech."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/s41591-018-0106-7","article-title":"Fetal gene therapy for neurodegenerative disease of infants","volume":"24","author":"Massaro","year":"2018","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1016\/S0002-9440(10)63566-3","article-title":"Viable mouse models of acid beta-glucosidase deficiency: The defect in Gaucher disease","volume":"163","author":"Xu","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1194\/jlr.M500202-JLR200","article-title":"Gaucher disease mouse models: Point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants","volume":"46","author":"Sun","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1073\/pnas.95.5.2503","article-title":"Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure (SIMP)","volume":"95","author":"Liu","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/2211-5463.12078","article-title":"Elevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models","volume":"6","author":"Kramer","year":"2016","journal-title":"FEBS Open Bio"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bcmd.2016.12.002","article-title":"Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease","volume":"68","author":"Murugesan","year":"2018","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2018.08.013","article-title":"The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson\u2019s disease patients and increases after lysosomal stress","volume":"120","author":"Moloney","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1471-4159.2012.07879.x","article-title":"Glucocerebrosidase mutations alter the endoplasmic reticulum and lysosomes in Lewy body disease","volume":"123","author":"Hanson","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/hmg\/ddx442","article-title":"Gaucher disease iPSC-derived osteoblasts have developmental and lysosomal defects that impair bone matrix deposition","volume":"27","author":"Panicker","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bcmd.2010.10.011","article-title":"Osteopenia in Gaucher disease develops early in life: Response to imiglucerase enzyme therapy in children, adolescents and adults","volume":"46","author":"Mistry","year":"2011","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10018","DOI":"10.1073\/pnas.1200941109","article-title":"Gaucher disease gene GBA functions in immune regulation","volume":"109","author":"Liu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","first-page":"1923","article-title":"Gaucher\u2019s disease. An unusual cause of intrathoracic extramedullary hematopoiesis","volume":"104","author":"Lynch","year":"1993","journal-title":"Chest"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s10545-010-9175-6","article-title":"Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy","volume":"33","author":"Stein","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1615\/CritRevOncog.2013006145","article-title":"Gaucher disease and malignancy: A model for cancer pathogenesis in an inborn error of metabolism","volume":"18","author":"Mistry","year":"2013","journal-title":"Crit. Rev. Oncog."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1002\/ajh.26675","article-title":"Cancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry","volume":"97","author":"Rosenbloom","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1182\/blood-2004-12-4672","article-title":"Gaucher disease and cancer incidence: A study from the Gaucher Registry","volume":"105","author":"Rosenbloom","year":"2005","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/path.4227","article-title":"B cell lymphoma and myeloma in murine Gaucher\u2019s disease","volume":"231","author":"Pavlova","year":"2013","journal-title":"J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1182\/blood-2014-09-600270","article-title":"Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation","volume":"125","author":"Nair","year":"2015","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1056\/NEJMoa1508808","article-title":"Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma","volume":"374","author":"Nair","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/hmg\/ddaf045","article-title":"Modeling Bone Marrow Microenvironment and Hematopoietic Dysregulation in Gaucher Disease through Vav-Cre Mediated GBA1 Deletion","volume":"34","author":"Belinsky","year":"2025","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Duffy, H.B.D., Byrnes, C., Zhu, H., Tuymetova, G., Lee, Y.T., Platt, F.M., and Proia, R.L. (2024). Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model. JCI Insight, 9.","DOI":"10.1172\/jci.insight.179126"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1073\/pnas.1400768111","article-title":"Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease","volume":"111","author":"Mistry","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2011.06.001","article-title":"Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies","volume":"146","author":"Mazzulli","year":"2011","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12101","DOI":"10.1073\/pnas.1108197108","article-title":"CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy","volume":"108","author":"Sardi","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9617","DOI":"10.1523\/JNEUROSCI.1525-17.2017","article-title":"Glucosylsphingosine Promotes alpha-Synuclein Pathology in Mutant GBA-Associated Parkinson\u2019s Disease","volume":"37","author":"Taguchi","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.neuron.2017.12.012","article-title":"Reversible Conformational Conversion of alpha-Synuclein into Toxic Assemblies by Glucosylceramide","volume":"97","author":"Zunke","year":"2018","journal-title":"Neuron"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ymgme.2020.01.009","article-title":"Glucosylsphingosine but not Saposin C, is the target antigen in Gaucher disease-associated gammopathy","volume":"129","author":"Nair","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e98259","DOI":"10.1172\/jci.insight.98259","article-title":"Antigen-mediated regulation in monoclonal gammopathies and myeloma","volume":"3","author":"Nair","year":"2018","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pavan, E., Ormazabal, M., Peruzzo, P., Vaena, E., Rozenfeld, P., and Dardis, A. (2020). CRISPR\/Cas9 Editing for Gaucher Disease Modelling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093268"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1038\/s41467-020-17148-x","article-title":"Engineering monocyte\/macrophage-specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing","volume":"11","author":"Scharenberg","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/infdis\/jiad141","article-title":"CRISPR Correction of the GBA Mutation in Human-Induced Pluripotent Stem Cells Restores Normal Function to Gaucher Macrophages and Increases Their Susceptibility to Mycobacterium tuberculosis","volume":"228","author":"Ramalingam","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1089\/hum.2018.072","article-title":"Delivery of Glucosylceramidase Beta Gene Using AAV9 Vector Therapy as a Treatment Strategy in Mouse Models of Gaucher Disease","volume":"30","author":"Du","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/hmg\/ddae113","article-title":"Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease","volume":"33","author":"Lin","year":"2024","journal-title":"Hum. Mol. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1172\/JCI29224","article-title":"Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility","volume":"116","author":"Yildiz","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1074\/jbc.M610544200","article-title":"Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2","volume":"282","author":"Boot","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ymgme.2007.08.001","article-title":"Secondary sphingolipid accumulation in a macrophage model of Gaucher disease","volume":"92","author":"Hein","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Marques, A.R., Aten, J., Ottenhoff, R., van Roomen, C.P., Herrera Moro, D., Claessen, N., Veloz, M.F.V., Zhou, K., Lin, Z., and Mirzaian, M. (2015). Reducing GBA2 activity ameliorates neuropathology in Niemann-Pick type C mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135889"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/1750-1172-8-151","article-title":"Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease","volume":"8","author":"Yildiz","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","article-title":"Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/cts.12911","article-title":"Assessment of Target Engagement in a First-in-Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders","volume":"14","author":"Gehin","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1001\/jamaneurol.2016.1593","article-title":"High Frequency of GBA Gene Mutations in Dementia With Lewy Bodies Among Ashkenazi Jews","volume":"73","author":"Shiner","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1474-4422(12)70190-4","article-title":"The link between the GBA gene and parkinsonism","volume":"11","author":"Sidransky","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13024-024-00713-z","article-title":"GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice","volume":"19","author":"Gregorio","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10719-021-10023-x","article-title":"Glycosphingolipid metabolism and its role in ageing and Parkinson\u2019s disease","volume":"39","author":"Wallom","year":"2022","journal-title":"Glycoconj. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"eabn3326","DOI":"10.1126\/sciadv.abn3326","article-title":"Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia","volume":"8","author":"Wang","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1073\/pnas.1221046110","article-title":"Histone deacetylase inhibitors increase glucocerebrosidase activity in Gaucher disease by modulation of molecular chaperones","volume":"110","author":"Yang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.ymthe.2017.08.004","article-title":"AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy","volume":"25","author":"Morabito","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"124","DOI":"10.12688\/wellcomeopenres.15329.1","article-title":"C57BL\/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo","volume":"4","author":"Clough","year":"2019","journal-title":"Wellcome Open Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1172\/JCI72308","article-title":"IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset","volume":"124","author":"Sag","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Atilano, M.L., Hull, A., Romila, C.A., Adams, M.L., Wildfire, J., Urena, E., Dyson, M., Ivan-Castillo-Quan, J., Partridge, L., and Kinghorn, K.J. (2023). Autophagic dysfunction and gut microbiota dysbiosis cause chronic immune activation in a Drosophila model of Gaucher disease. PLoS Genet., 19.","DOI":"10.1371\/journal.pgen.1011063"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"eadk1296","DOI":"10.1126\/sciadv.adk1296","article-title":"The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1","volume":"10","author":"Gustavsson","year":"2024","journal-title":"Sci. Adv."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:40:21Z","timestamp":1765442421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":82,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411915"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411915","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,12,10]]}}}