{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:12:35Z","timestamp":1779189155910,"version":"3.51.4"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T00:00:00Z","timestamp":1394755200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0091952","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T20:43:28Z","timestamp":1394829808000},"page":"e91952","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Monoallelic Germline TSC1 Mutations Are Permissive for T Lymphocyte Development and Homeostasis in Tuberous Sclerosis Complex Individuals"],"prefix":"10.1371","volume":"9","author":[{"given":"Karolina","family":"Pilipow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Basso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Migone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Mondino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,3,14]]},"reference":[{"key":"ref1","first-page":"R251","article-title":"Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 14 Spec No","volume":"2","author":"DJ Kwiatkowski","year":"2005"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1365-4632.2010.04727.x","article-title":"Tuberous sclerosis complex: tumors and tumorigenesis","volume":"50","author":"J Borkowska","year":"2011","journal-title":"Int J Dermatol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jaad.2007.05.004","article-title":"Tuberous sclerosis complex: advances in diagnosis, genetics, and management","volume":"57","author":"RA Schwartz","year":"2007","journal-title":"J Am Acad Dermatol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1001\/archneur.1994.00540130110018","article-title":"Tuberous sclerosis in Western Sweden. A population study of cases with early childhood onset","volume":"51","author":"G Ahlsen","year":"1994","journal-title":"Arch Neurol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","article-title":"The tuberous sclerosis complex","volume":"355","author":"PB Crino","year":"2006","journal-title":"N Engl J Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/S1072-7515(98)00239-7","article-title":"The tuberous sclerosis complex: a comprehensive review","volume":"187","author":"DM Weiner","year":"1998","journal-title":"J Am Coll Surg"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1749-6632.2009.05117.x","article-title":"The tuberous sclerosis complex","volume":"1184","author":"KA Orlova","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1055\/s-0030-1269906","article-title":"Tuberous sclerosis complex: neurological, renal and pulmonary manifestations","volume":"41","author":"DN Franz","year":"2010","journal-title":"Neuropediatrics"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/ng0294-193","article-title":"Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients","volume":"6","author":"AJ Green","year":"1994","journal-title":"Nat Genet"},{"key":"ref10","first-page":"400","article-title":"Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions","volume":"59","author":"EP Henske","year":"1996","journal-title":"Am J Hum Genet"},{"key":"ref11","first-page":"1639","article-title":"Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors","volume":"151","author":"EP Henske","year":"1997","journal-title":"Am J Pathol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s004010050587","article-title":"Tuberous sclerosis-like lesions in epileptogenic human neocortex lack allelic loss at the TSC1 and TSC2 regions","volume":"93","author":"HK Wolf","year":"1997","journal-title":"Acta Neuropathol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1086\/321972","article-title":"Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions","volume":"69","author":"Y Niida","year":"2001","journal-title":"Am J Hum Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1093\/jnen\/63.12.1236","article-title":"Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation","volume":"63","author":"JA Chan","year":"2004","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1212\/WNL.0b013e3181e04325","article-title":"Biallelic TSC gene inactivation in tuberous sclerosis complex","volume":"74","author":"PB Crino","year":"2010","journal-title":"Neurology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1034\/j.1399-0004.2002.620501.x","article-title":"Pathogenesis of hereditary tumors: beyond the &quot;two-hit&quot; hypothesis","volume":"62","author":"T Tucker","year":"2002","journal-title":"Clin Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/modpathol.2010.114","article-title":"Loss of heterozygosity on tuberous sclerosis complex genes in multifocal micronodular pneumocyte hyperplasia","volume":"23","author":"T Hayashi","year":"2010","journal-title":"Mod Pathol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1471-2350-12-29","article-title":"Evidence for population variation in TSC1 and TSC2 gene expression","volume":"12","author":"GM Jentarra","year":"2011","journal-title":"BMC Med Genet"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1038\/nn1566","article-title":"Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2","volume":"8","author":"SF Tavazoie","year":"2005","journal-title":"Nat Neurosci"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1084\/jem.20081297","article-title":"TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species","volume":"205","author":"C Chen","year":"2008","journal-title":"J Exp Med"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Yang K, Neale G, Green DR, He W, Chi H (2011) The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat Immunol.","DOI":"10.1038\/ni.2068"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1002\/eji.201141411","article-title":"Regulation of T-cell survival and mitochondrial homeostasis by TSC1","volume":"41","author":"TF O'Brien","year":"2011","journal-title":"Eur J Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.4049\/jimmunol.1003968","article-title":"The tuberous sclerosis complex-mammalian target of rapamycin pathway maintains the quiescence and survival of naive T cells","volume":"187","author":"Q Wu","year":"2011","journal-title":"J Immunol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e30592","DOI":"10.1371\/journal.pone.0030592","article-title":"TSC1\/2 signaling complex is essential for peripheral naive CD8+ T cell survival and homeostasis in mice","volume":"7","author":"L Zhang","year":"2012","journal-title":"PLoS One"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/prot.20810","article-title":"Prediction of protein stability changes for single-site mutations using support vector machines","volume":"62","author":"J Cheng","year":"2006","journal-title":"Proteins"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.bbadis.2010.06.004","article-title":"Analysis of TSC1 truncations defines regions involved in TSC1 stability, aggregation and interaction","volume":"1802","author":"M Hoogeveen-Westerveld","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/humu.21451","article-title":"Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex","volume":"32","author":"M Hoogeveen-Westerveld","year":"2011","journal-title":"Hum Mutat"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1182\/blood-2008-05-156059","article-title":"IL-7 and IL-15 allow the generation of suicide gene-modified alloreactive self-renewing central memory human T lymphocytes","volume":"113","author":"S Kaneko","year":"2009","journal-title":"Blood"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.bbrc.2005.08.020","article-title":"Heme oxygenase and heme degradation","volume":"338","author":"G Kikuchi","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1471-4159.2012.07914.x","article-title":"Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment","volume":"123","author":"W Song","year":"2012","journal-title":"J Neurochem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.coi.2010.01.018","article-title":"Metabolism in T cell activation and differentiation","volume":"22","author":"EL Pearce","year":"2010","journal-title":"Curr Opin Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e20107","DOI":"10.1371\/journal.pone.0020107","article-title":"Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells","volume":"6","author":"S He","year":"2011","journal-title":"PLoS One"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/emmm.201100131","article-title":"Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis","volume":"3","author":"NA Neuman","year":"2011","journal-title":"EMBO Mol Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.ccr.2010.10.019","article-title":"FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis","volume":"18","author":"B Gan","year":"2010","journal-title":"Cancer Cell"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1101\/gad.1314605","article-title":"Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2","volume":"19","author":"BD Manning","year":"2005","journal-title":"Genes Dev"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/hmg\/ddq491","article-title":"Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex","volume":"20","author":"LH Zeng","year":"2011","journal-title":"Hum Mol Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","article-title":"A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells","volume":"11","author":"DJ Kwiatkowski","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"6178","DOI":"10.4049\/jimmunol.169.11.6178","article-title":"Clonal anergy is maintained independently of T cell proliferation","volume":"169","author":"S Colombetti","year":"2002","journal-title":"J Immunol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1106148","article-title":"Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex","volume":"307","author":"DD Sarbassov","year":"2005","journal-title":"Science"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0218354","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000}}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0091952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T15:56:08Z","timestamp":1540223768000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0091952"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Powell","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,3,14]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,3,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0091952","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0218354","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,14]]}}}