Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse.

Human Molecular Genetics
Sharon W WayMichael J Gambello

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant, tumor predisposition disorder characterized by significant neurodevelopmental brain lesions, such as tubers and subependymal nodules. The neuropathology of TSC is often associated with seizures and intellectual disability. To learn about the developmental perturbations that lead to these brain lesions, we created a mouse model that selectively deletes the Tsc2 gene from radial glial progenitor cells in the developing cerebral cortex and hippocampus. These Tsc2 mutant mice were severely runted, developed post-natal megalencephaly and died between 3 and 4 weeks of age. Analysis of brain pathology demonstrated cortical and hippocampal lamination defects, hippocampal heterotopias, enlarged dysplastic neurons and glia, abnormal myelination and an astrocytosis. These histologic abnormalities were accompanied by activation of the mTORC1 pathway as assessed by increased phosphorylated S6 in brain lysates and tissue sections. Developmental analysis demonstrated that loss of Tsc2 increased the subventricular Tbr2-positive basal cell progenitor pool at the expense of early born Tbr1-positive post-mitotic neurons. These results establish the novel concept that loss of function of T...Continue Reading

References

Dec 31, 1993·Cell·UNKNOWN European Chromosome 16 Tuberous Sclerosis Consortium
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·P B CrinoJ Eberwine
Aug 8, 1997·Science·M van SlegtenhorstD J Kwiatkowski
Aug 1, 1997·Acta Neuropathologica·S H ParkH V Vinters
Oct 2, 1998·Acta Radiologica·P D GriffithsC Verity
Nov 14, 1998·Journal of Autism and Developmental Disorders·S L Smalley
Sep 24, 1999·The Journal of Clinical Investigation·H OndaD J Kwiatkowski
Oct 13, 2000·Human Genetics·J P CheadleD J Kwiatkowski
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·T KobayashiO Hino
Oct 23, 2001·Genesis : the Journal of Genetics and Development·L ZhuoA Messing
Apr 26, 2002·Trends in Neurosciences·Kenneth Campbell, Magdalena Götz
Aug 13, 2002·Nature Cell Biology·Xinsheng GaoDuojia Pan
Dec 31, 2002·Journal of Child Neurology·Paolo GalluzziCarlo Venturi
Mar 12, 2003·Neuron·Paolo MalatestaMagdalena Götz
Apr 11, 2003·The Journal of Comparative Neurology·Russell J FerlandChristopher A Walsh
May 29, 2003·Nature Cell Biology·Yong ZhangDuojia Pan
Jan 3, 2004·Nature Neuroscience·Stephen C NoctorArnold R Kriegstein
Feb 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wulf HaubensakWieland B Huttner
Jul 9, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yasushi OhkuboFlora M Vaccarino
Sep 29, 2004·The Journal of Comparative Neurology·Marta NietoChristopher A Walsh
Nov 24, 2004·Pediatric Research·Heidi KenersonRaymond S Yeung
Nov 26, 2004·Journal of Child Neurology·Francis J DiMario
Nov 26, 2004·Journal of Child Neurology·Penny Prather, Petrus J de Vries
Nov 26, 2004·Journal of Child Neurology·Elizabeth Anne Thiele
Nov 26, 2004·Journal of Child Neurology·Peter B Crino
Nov 26, 2004·Journal of Child Neurology·Danielle K Scheidenhelm, David H Gutmann
Dec 4, 2004·Genes, Chromosomes & Cancer·Laifong LeeSandra L Dabora
Dec 31, 2004·Journal of Neuropathology and Experimental Neurology·Jennifer A ChanDavid J Kwiatkowski
Jan 7, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chris EnglundRobert F Hevner
Apr 23, 2005·Glia·Milos Pekny, Michael Nilsson

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Citations

Apr 2, 2010·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Romina MoaveroPaolo Curatolo
Feb 7, 2013·Acta Neuropathologica·Peter B Crino
May 1, 2012·Current Neurology and Neuroscience Reports·Robin C C Ryther, Michael Wong
Jul 16, 2013·Current Treatment Options in Neurology·Darcy A Krueger
Oct 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·June GotoDavid J Kwiatkowski
Oct 6, 2011·Current Opinion in Pediatrics·Omar S Khwaja, Mustafa Sahin
Feb 9, 2011·Current Opinion in Neurology·Peter Tsai, Mustafa Sahin
Apr 29, 2010·The Journal of Clinical Investigation·Ksenia A OrlovaPeter B Crino
Mar 16, 2011·The Journal of Clinical Investigation·David M FelicianoAngélique Bordey
Jun 8, 2013·Disease Models & Mechanisms·Laura MagriRossella Galli
May 23, 2013·PloS One·Shilpa PrabhakarXandra O Breakefield
Jun 17, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Helen S BateupBernardo L Sabatini
Feb 9, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carlos A LafourcadeAngélique Bordey
Feb 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Paul S Buckmaster, Felicia H Lew
Sep 25, 2012·Journal of Neurosurgery. Pediatrics·Tracy S MaChad Carlson
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Mar 1, 2012·Epilepsy Currents·Michael Wong
Oct 20, 2012·Cerebral Cortex·Victoria TsaiPeter B Crino
Nov 6, 2012·Cellular and Molecular Life Sciences : CMLS·Laura Magri, Rossella Galli
Feb 19, 2011·FEBS Letters·Juliette M Han, Mustafa Sahin
Feb 7, 2016·Seminars in Cell & Developmental Biology·Andrew R TeeJoseph M Bateman
Apr 26, 2015·Journal of Neuroscience Methods·Michael Wong, Steven N Roper
Feb 4, 2014·Pediatric Neurology·Kristina Jülich, Mustafa Sahin
Sep 6, 2011·Trends in Molecular Medicine·Peter B Crino
Jan 7, 2016·Frontiers in Molecular Neuroscience·Anne BieverEmma Puighermanal
Jan 24, 2015·Biochemical and Biophysical Research Communications·Natalia S RozasPramod K Dash
Jun 1, 2009·Journal of Neurodevelopmental Disorders·Kevin C Ess
Jun 12, 2013·The Journal of Comparative Neurology·Ulrike MietzschMichael J Gambello

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Methods Mentioned

BETA
GTPase
transgenic
imaging techniques
PCR
genotyping

Software Mentioned

SPSS
Photoshop
Adobe Photoshop
ImageJ
Excel

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