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Using Cre\/Lox mouse models, we found that astrocyte-specific deletion of\n                    <jats:italic>Sumf1<\/jats:italic>\n                    in vivo induced severe lysosomal storage and autophagy dysfunction with consequential cytoplasmic accumulation of autophagic substrates. Lysosomal storage in astrocytes was sufficient to induce degeneration of cortical neurons in vivo. Furthermore, in an ex vivo coculture assay, we observed that\n                    <jats:italic>Sumf1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    astrocytes failed to support the survival and function of wild-type cortical neurons, suggesting a non-cell autonomous mechanism for neurodegeneration. Compared with the astrocyte-specific deletion of\n                    <jats:italic>Sumf1<\/jats:italic>\n                    , the concomitant removal of\n                    <jats:italic>Sumf1<\/jats:italic>\n                    in both neurons and glia in vivo induced a widespread neuronal loss and robust neuroinflammation. Finally, behavioral analysis of mice with astrocyte-specific deletion of\n                    <jats:italic>Sumf1<\/jats:italic>\n                    compared with mice with\n                    <jats:italic>Sumf1<\/jats:italic>\n                    deletion in both astrocytes and neurons allowed us to link a subset of neurological manifestations of MSD to astrocyte dysfunction. This study indicates that astrocytes are integral components of the neuropathology in MSD and that modulation of astrocyte function may impact disease course.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1209577109","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T00:48:19Z","timestamp":1343090899000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":109,"title":["Astrocyte dysfunction triggers neurodegeneration in a lysosomal storage disorder"],"prefix":"10.1073","volume":"109","author":[{"given":"Chiara","family":"Di Malta","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, 80131 Naples, Italy;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX 77030;"},{"name":"The Open University, Milton Keynes MK76AA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Fryer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Settembre","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, 80131 Naples, Italy;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ballabio","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, 80131 Naples, Italy;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX 77030;"},{"name":"Medical Genetics, Department of Pediatrics, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,7,23]]},"reference":[{"key":"e_1_1_2_17_10_1_2","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2009.11.3\/mbelanger"},{"key":"e_1_1_2_17_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0355"},{"key":"e_1_1_2_17_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1725"},{"key":"e_1_1_2_17_10_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.6.080604.162334"},{"key":"e_1_1_2_17_10_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31097"},{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00348-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.6.080604.162334"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198508786.003.0003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.12.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm289"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20207"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.3.365"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(99)00137-0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.016"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04723"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04724"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4846"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.21.5720"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64369-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.01.021"},{"key":"e_1_3_3_16_2","first-page":"3373","article-title":"The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice","volume":"119","author":"Weidemann A","year":"2009","unstructured":"A Weidemann, et al., The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. 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