{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:36:22Z","timestamp":1770910582746,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,1]]},"DOI":"10.1093\/hmg\/ddp176","type":"journal-article","created":{"date-parts":[[2009,4,9]],"date-time":"2009-04-09T01:06:30Z","timestamp":1239239190000},"page":"2378-2387","source":"Crossref","is-referenced-by-count":27,"title":["A hypomorphic allele of Tsc2 highlights the role of TSC1\/TSC2 in signaling to AKT and models mild human TSC2 alleles"],"prefix":"10.1093","volume":"18","author":[{"given":"Kristen","family":"Pollizzi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabela","family":"Malinowska-Kolodziej","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Doughty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Betz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"June","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,4,8]]},"reference":[{"key":"key\n\t\t\t\t20170522141805_DDP176C1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","article-title":"The tuberous sclerosis complex","volume":"355","author":"Crino","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"key\n\t\t\t\t20170522141805_DDP176C2","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195122107.001.0001","volume-title":"The Tuberous Sclerosis Complex","author":"Gomez","year":"1999","edition":"3rd edn."},{"key":"key\n\t\t\t\t20170522141805_DDP176C3","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1528-1167.2007.01035.x","article-title":"Tuberous sclerosis complex and epilepsy: recent developments and future challenges","volume":"48","author":"Holmes","year":"2007","journal-title":"Epilepsia"},{"key":"key\n\t\t\t\t20170522141805_DDP176C4","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1378\/chest.07-0898","article-title":"Lymphangioleiomyomatosis: a clinical update","volume":"133","author":"McCormack","year":"2008","journal-title":"Chest"},{"key":"key\n\t\t\t\t20170522141805_DDP176C5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1111\/j.1523-1755.2004.00838.x","article-title":"Renal angiomyolipomata","volume":"66","author":"Bissler","year":"2004","journal-title":"Kidney Int."},{"key":"key\n\t\t\t\t20170522141805_DDP176C6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s004390000348","article-title":"Molecular genetic advances in tuberous sclerosis","volume":"107","author":"Cheadle","year":"2000","journal-title":"Hum. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/sj.ejhg.5201276","article-title":"Distinct effects of single amino-acid changes to tuberin on the function of the tuberin\u2013hamartin complex","volume":"13","author":"Nellist","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1471-2350-9-10","article-title":"Functional characterisation of the TSC1\u2013TSC2 complex to assess multiple TSC2 variants identified in single families affected by tuberous sclerosis complex","volume":"9","author":"Nellist","year":"2008","journal-title":"BMC Med. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C9","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/ana.21037","article-title":"Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation","volume":"60","author":"Jansen","year":"2006","journal-title":"Ann. Neurol."},{"key":"key\n\t\t\t\t20170522141805_DDP176C10","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/jmg.38.5.347","article-title":"A novel missense mutation in the GTPase activating protein homology region of TSC2 in two large families with tuberous sclerosis complex","volume":"38","author":"Khare","year":"2001","journal-title":"J. Med. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1212\/01.WNL.0000073272.47681.BB","article-title":"A family with seizures and minor features of tuberous sclerosis and a novel TSC2 mutation","volume":"61","author":"O\u2019Connor","year":"2003","journal-title":"Neurology"},{"issue":"Spec no. 2","key":"key\n\t\t\t\t20170522141805_DDP176C12","doi-asserted-by":"crossref","first-page":"R251","DOI":"10.1093\/hmg\/ddi260","article-title":"Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways","volume":"14","author":"Kwiatkowski","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1\u2013TSC2 complex: a molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"key\n\t\t\t\t20170522141805_DDP176C14","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1083\/jcb.200403069","article-title":"The TSC1\u20132 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins","volume":"166","author":"Harrington","year":"2004","journal-title":"J. Cell Biol."},{"key":"key\n\t\t\t\t20170522141805_DDP176C15","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1172\/JCI200317222","article-title":"Loss of Tsc1\/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR","volume":"112","author":"Zhang","year":"2003","journal-title":"J. Clin. Invest."},{"key":"key\n\t\t\t\t20170522141805_DDP176C16","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.1128\/MCB.00289-08","article-title":"The TSC1\u2013TSC2 complex is required for proper activation of mTOR complex 2","volume":"28","author":"Huang","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"key\n\t\t\t\t20170522141805_DDP176C17","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI7319","article-title":"Tsc2(+\/\u2212) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background","volume":"104","author":"Onda","year":"1999","journal-title":"J. Clin. Invest."},{"key":"key\n\t\t\t\t20170522141805_DDP176C18","first-page":"1206","article-title":"Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice","volume":"59","author":"Kobayashi","year":"1999","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170522141805_DDP176C19","doi-asserted-by":"crossref","first-page":"8762","DOI":"10.1073\/pnas.151033798","article-title":"A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice","volume":"98","author":"Kobayashi","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170522141805_DDP176C20","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":"Kwiatkowski","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C21","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1093\/hmg\/ddi190","article-title":"A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma","volume":"14","author":"Wilson","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C22","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/dvg.20271","article-title":"Generation of a conditional disruption of the Tsc2 gene","volume":"45","author":"Hernandez","year":"2007","journal-title":"Genesis"},{"key":"key\n\t\t\t\t20170522141805_DDP176C23","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1128\/MCB.01695-07","article-title":"Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice","volume":"28","author":"Shigeyama","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"key\n\t\t\t\t20170522141805_DDP176C24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/hmg\/ddi039","article-title":"A mouse model of cardiac rhabdomyoma generated by loss of Tsc1 in ventricular myocytes","volume":"14","author":"Meikle","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522141805_DDP176C25","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-88418-4","volume-title":"The House Mouse: Atlas of Embryonic Development","author":"Theiler","year":"1989"},{"key":"key\n\t\t\t\t20170522141805_DDP176C26","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/dvdy.1199","article-title":"Early expression of endomucin on endothelium of the mouse embryo and on putative hematopoietic clusters in the dorsal aorta","volume":"222","author":"Brachtendorf","year":"2001","journal-title":"Dev. Dyn."},{"key":"key\n\t\t\t\t20170522141805_DDP176C27","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":"Sarbassov","year":"2005","journal-title":"Science"},{"key":"key\n\t\t\t\t20170522141805_DDP176C28","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1172\/JCI28984","article-title":"PDGF receptors are critical for PI3K\/AKT activation and negatively regulated by mTOR","volume":"117","author":"Zhang","year":"2007","journal-title":"J. Clin. Inv."},{"key":"key\n\t\t\t\t20170522141805_DDP176C29","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.cub.2004.08.026","article-title":"Inappropriate activation of the TSC\/Rheb\/mTOR\/S6K cassette induces IRS1\/2 depletion, insulin resistance, and cell survival deficiencies","volume":"14","author":"Shah","year":"2004","journal-title":"Curr. Biol."},{"key":"key\n\t\t\t\t20170522141805_DDP176C30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.molcel.2006.03.029","article-title":"Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt\/PKB","volume":"22","author":"Sarbassov","year":"2006","journal-title":"Mol. Cell"},{"key":"key\n\t\t\t\t20170522141805_DDP176C31","doi-asserted-by":"crossref","first-page":"10407","DOI":"10.1128\/MCB.25.23.10407-10418.2005","article-title":"Dosage-dependent effects of Akt1\/protein kinase Balpha (PKBalpha) and Akt3\/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice","volume":"25","author":"Yang","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"key\n\t\t\t\t20170522141805_DDP176C32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa063564","article-title":"Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis","volume":"358","author":"Bissler","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"key\n\t\t\t\t20170522141805_DDP176C33","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1101\/gad.13.23.3136","article-title":"Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch","volume":"13","author":"Trumpp","year":"1999","journal-title":"Genes Dev."},{"key":"key\n\t\t\t\t20170522141805_DDP176C34","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1158\/0008-5472.CAN-04-3840","article-title":"Estrogen enhances whereas tamoxifen retards development of Tsc mouse liver hemangioma: a tumor related to renal angiomyolipoma and pulmonary lymphangioleiomyomatosis","volume":"65","author":"El-Hashemite","year":"2005","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170522141805_DDP176C35","doi-asserted-by":"crossref","first-page":"5546","DOI":"10.1523\/JNEUROSCI.5540-06.2007","article-title":"A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival","volume":"27","author":"Meikle","year":"2007","journal-title":"J. Neurosci."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/18\/13\/2378\/17246635\/ddp176.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T13:59:10Z","timestamp":1710251950000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article-lookup\/doi\/10.1093\/hmg\/ddp176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,8]]},"references-count":35,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2009,4,8]]},"published-print":{"date-parts":[[2009,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddp176","relation":{},"ISSN":["1460-2083","0964-6906"],"issn-type":[{"value":"1460-2083","type":"electronic"},{"value":"0964-6906","type":"print"}],"subject":[],"published":{"date-parts":[[2009,4,8]]}}}