{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:52:54Z","timestamp":1761742374973},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,4,30]],"date-time":"2004-04-30T00:00:00Z","timestamp":1083283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Individuals with tuberous sclerosis complex (TSC) develop central nervous system abnormalities that may reflect astrocyte dysfunction. In an effort to model astrocyte dysfunction in TSC, we generated mice lacking <jats:italic>Tsc1<\/jats:italic> (hamartin) expression in astrocytes and demonstrated that <jats:italic>Tsc1<\/jats:italic>\u2010null astrocytes exhibit abnormalities in contact inhibition growth arrest. In this study, we demonstrate that hamartin\u2010deficient astrocytes are also defective in cell size regulation. We show that the increase in <jats:italic>Tsc1<\/jats:italic>\u2010null astrocyte size is associated with increased activation of the S6\u2010kinase pathway. In keeping with recent reports that the hamartin\/tuberin complex may regulate Rheb and downstream S6K activation, we demonstrate that expression of either Rheb or S6K in primary astrocytes results in increased S6 pathway activation, and that inhibition of Rheb activity in <jats:italic>Tsc1<\/jats:italic>\u2010deficient astrocytes using either pharmacologic or genetic strategies markedly reduces S6 activation. Collectively, these observations suggest that <jats:italic>TSC<\/jats:italic> inactivation in astrocytes results in defective cell size regulation associated with dysregulated Rheb\/mTOR\/S6K pathway activity. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20036","type":"journal-article","created":{"date-parts":[[2004,4,30]],"date-time":"2004-04-30T16:03:08Z","timestamp":1083340988000},"page":"180-188","source":"Crossref","is-referenced-by-count":62,"title":["Loss of tuberous sclerosis complex 1 (<i>Tsc1<\/i>) expression results in increased Rheb\/S6K pathway signaling important for astrocyte cell size regulation"],"prefix":"10.1002","volume":"47","author":[{"given":"Erik J.","family":"Uhlmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle 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