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We conditionally deleted the GBA1 gene in hematopoietic and mesenchymal cell lineages using an Mx1 promoter. Although this mouse fully recapitulated human GD1, cytokine measurements, microarray analysis, and cellular immunophenotyping together revealed widespread dysfunction not only of macrophages, but also of thymic T cells, dendritic cells, and osteoblasts. The severe osteoporosis was caused by a defect in osteoblastic bone formation arising from an inhibitory effect of the accumulated lipids LysoGL-1 and GL-1 on protein kinase C. This study provides direct evidence for the involvement in GD1 of multiple cell lineages, suggesting that cells other than macrophages may be worthwhile therapeutic targets.<\/jats:p>","DOI":"10.1073\/pnas.1003308107","type":"journal-article","created":{"date-parts":[[2010,10,20]],"date-time":"2010-10-20T23:15:59Z","timestamp":1287616559000},"page":"19473-19478","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":215,"title":["Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage"],"prefix":"10.1073","volume":"107","author":[{"given":"Pramod K.","family":"Mistry","sequence":"first","affiliation":[{"name":"Departments of aPediatrics,"},{"name":"Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of aPediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of aPediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Nottoli","sequence":"additional","affiliation":[{"name":"Comparative Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McGrath","sequence":"additional","affiliation":[{"name":"Departments of aPediatrics,"},{"name":"Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanpat","family":"Jain","sequence":"additional","affiliation":[{"name":"Pathology, Yale School of Medicine, New Haven, CT 06562;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genzyme, Framingham, MA 02134;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Keutzer","sequence":"additional","affiliation":[{"name":"Genzyme, Framingham, MA 02134;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Lien","family":"Chuang","sequence":"additional","affiliation":[{"name":"Genzyme, Framingham, MA 02134;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajahat Z.","family":"Mehal","sequence":"additional","affiliation":[{"name":"Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yale School of Public Health and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Lin","sequence":"additional","affiliation":[{"name":"Yale School of Public Health and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikant","family":"Mane","sequence":"additional","affiliation":[{"name":"Keck Center for Genomics, Yale School of Medicine, New Haven, CT 06562;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY 10029; 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