{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:28:57Z","timestamp":1787005737237,"version":"build-2736575974"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,10,14]]},"abstract":"<jats:p>\n                    The palmitoyl protein thioesterase-2 (\n                    <jats:italic>PPT2<\/jats:italic>\n                    ) gene encodes a lysosomal thioesterase homologous to PPT1, which is the enzyme defective in the human disorder called infantile neuronal ceroid lipofuscinosis. In this article, we report that PPT2 deficiency in mice causes an unusual form of neuronal ceroid lipofuscinosis with striking visceral manifestations. All PPT2-deficient mice displayed a neurodegenerative phenotype with spasticity and ataxia by 15 mo. The bone marrow was infiltrated by brightly autofluorescent macrophages and multinucleated giant cells, but interestingly, the macrophages did not have the typical appearance of foam cells commonly associated with other lysosomal storage diseases. Marked splenomegaly caused by extramedullary hematopoiesis was observed. The pancreas was grossly orange to brown as a result of massive storage of lipofuscin pigments in the exocrine (but not islet) cells. Electron microscopy showed that the storage material consisted of multilamellar membrane profiles (\u201czebra bodies\u201d). In summary, PPT2 deficiency in mice manifests as a neurodegenerative disorder with visceral features. Although PPT2 deficiency has not been described in humans, manifestations would be predicted to include neurodegeneration with bone marrow histiocytosis, visceromegaly, brown pancreas, and linkage to chromosome 6p21.3 in affected families.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2033229100","type":"journal-article","created":{"date-parts":[[2003,10,14]],"date-time":"2003-10-14T15:05:46Z","timestamp":1066143946000},"page":"12325-12330","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["Disruption of\n                    <i>PPT2<\/i>\n                    in mice causes an unusual lysosomal storage disorder with neurovisceral features"],"prefix":"10.1073","volume":"100","author":[{"given":"Praveena","family":"Gupta","sequence":"first","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail A.","family":"Soyombo","sequence":"additional","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Shelton","sequence":"additional","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian G.","family":"Wilkofsky","sequence":"additional","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystyna E.","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Richardson","sequence":"additional","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Hofmann","sequence":"additional","affiliation":[{"name":"The Hamon Center for Therapeutic Oncology Research, Division of Cardiology, Department of Internal Medicine, and Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and Department of Neurology, State University of New York\/Health Science Center, Brooklyn, NY 11203"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,10,3]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/376584a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200112000-00019"},{"key":"e_1_3_2_3_2","unstructured":"Goebel H. 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